<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02220894</url>
  </required_header>
  <id_info>
    <org_study_id>3475-042</org_study_id>
    <secondary_id>152877</secondary_id>
    <secondary_id>MK-3475-042</secondary_id>
    <secondary_id>KEYNOTE-042</secondary_id>
    <secondary_id>2014-001473-14</secondary_id>
    <nct_id>NCT02220894</nct_id>
  </id_info>
  <brief_title>Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)</brief_title>
  <official_title>A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) Versus Platinum Based Chemotherapy in Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small&#xD;
      cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to&#xD;
      35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel&#xD;
      or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based&#xD;
      chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance&#xD;
      therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that&#xD;
      pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants&#xD;
      enrolled in the global study, 92 were also enrolled in the China extension study for&#xD;
      MK-3475-042 (NCT03850444).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2014</start_date>
  <completion_date type="Actual">September 12, 2022</completion_date>
  <primary_completion_date type="Actual">February 26, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced At Least One Adverse Event (AE)</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)</measure>
    <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
    <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1274</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SOC Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 IV on Day 1 of every 21-day cycle (Q3W) for a maximum of 6 cycles OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 IV on Day 1 Q3W for a maximum of 6 cycles; participants with non-squamous histologies may go on to receive optional treatment with pemetrexed 500 mg/m^2 IV on Day 1 Q3W.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>carboplatin</intervention_name>
    <arm_group_label>SOC Treatment</arm_group_label>
    <other_name>PARAPLATIN®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel</intervention_name>
    <arm_group_label>SOC Treatment</arm_group_label>
    <other_name>TAXOL®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pemetrexed</intervention_name>
    <arm_group_label>SOC Treatment</arm_group_label>
    <other_name>ALIMTA®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC&#xD;
&#xD;
          -  PD-L1 positive tumor&#xD;
&#xD;
          -  Measureable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  No prior systemic chemotherapy for the treatment of the participant's advanced or&#xD;
             metastatic disease (treatment with chemotherapy and/or radiation as part of&#xD;
             neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior&#xD;
             to diagnosis of advanced or metastatic disease)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  No prior malignancy, with the exception of basal cell carcinoma of the skin,&#xD;
             superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or&#xD;
             has undergone potentially curative therapy with no evidence of that disease recurrence&#xD;
             for 5 years since initiation of that therapy&#xD;
&#xD;
          -  Submission of formalin-fixed diagnostic tumor tissue (in the case of participants&#xD;
             having received adjuvant systemic therapy, the tissue should be taken after completion&#xD;
             of this therapy)&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative urine or serum&#xD;
             pregnancy test and must be willing to use two adequate barrier methods of&#xD;
             contraception or a barrier method plus a hormonal method starting with the screening&#xD;
             visit through 120 days after the last dose of pembrolizumab or 180 days after the last&#xD;
             dose of chemotherapeutic agents used in the study&#xD;
&#xD;
          -  Male participants with a female partner(s) of child-bearing potential must be willing&#xD;
             to use two adequate barrier methods of contraception from screening through 120 days&#xD;
             after the last dose of pembrolizumab or 180 days after the last dose of&#xD;
             chemotherapeutic agents used in the study&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm&#xD;
             microtubule-associated protein-like 4(EML4) gene/anaplastic lymphoma kinase (ALK) gene&#xD;
             fusion positive&#xD;
&#xD;
          -  Currently participating or has participated in a study of an investigational agent or&#xD;
             using an investigational device within 4 weeks of the first dose of study therapy&#xD;
&#xD;
          -  No tumor specimen evaluable for PD-L1 expression by the central study laboratory&#xD;
&#xD;
          -  Squamous histology and received carboplatin in combination with paclitaxel in the&#xD;
             adjuvant setting&#xD;
&#xD;
          -  Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy&#xD;
             or receiving any other form of immunosuppressive medication with the exception of&#xD;
             daily steroid replacement therapy&#xD;
&#xD;
          -  The NSCLC can be treated with curative intent with either surgical resection and/or&#xD;
             chemoradiation&#xD;
&#xD;
          -  Expected to require any other form of systemic or localized antineoplastic therapy&#xD;
             while on study&#xD;
&#xD;
          -  Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within&#xD;
             3 weeks of the first dose of study therapy; received lung radiation therapy &gt;30 Gy&#xD;
             within 6 months of the first dose of study therapy&#xD;
&#xD;
          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic&#xD;
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other&#xD;
             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)&#xD;
&#xD;
          -  Known central nervous system metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
&#xD;
          -  Had allogeneic tissue/solid organ transplantation&#xD;
&#xD;
          -  Interstitial lung disease or history of pneumonitis that has required oral or IV&#xD;
             steroids&#xD;
&#xD;
          -  Has received or will receive a live vaccine within 30 days prior to the first study&#xD;
             therapy (seasonal flu vaccines that do not contain live vaccine are permitted)&#xD;
&#xD;
          -  Active infection requiring intravenous systemic therapy&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Known active Hepatitis B or C&#xD;
&#xD;
          -  Regular user (including &quot;recreational use&quot;) of any illicit drugs or had a recent&#xD;
             history (within the last year) of substance abuse (including alcohol)&#xD;
&#xD;
          -  Pregnant, breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Argentina</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>China</country>
    <country>Colombia</country>
    <country>Czech Republic</country>
    <country>Estonia</country>
    <country>Guatemala</country>
    <country>Hong Kong</country>
    <country>Hungary</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>Mexico</country>
    <country>Peru</country>
    <country>Philippines</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>Vietnam</country>
  </removed_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinicial Trials Information</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <results_first_submitted>February 14, 2019</results_first_submitted>
  <results_first_submitted_qc>March 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 15, 2019</results_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PD-1</keyword>
  <keyword>PD1</keyword>
  <keyword>PD-L1</keyword>
  <keyword>PDL1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 9, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT02220894/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Of the 1275 participants randomized (pembrolizumab=638, chemotherapy=637), 1 participant assigned to receive pembrolizumab died prior to randomization and was randomized in error. The intent to treat population was defined as participants alive at the time of randomization, so the actual randomized population included 637 participants in each arm.</recruitment_details>
      <pre_assignment_details>These interim results are based on a database cutoff date of 26-February-2018, at which time 448 participants were ongoing in the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles)</description>
        </group>
        <group group_id="P2">
          <title>Chemotherapy (Standard of Care [SOC] Treatment)</title>
          <description>Participants received carboplatin at target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="637">1 additional participant was randomized in error</participants>
                <participants group_id="P2" count="637"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="636"/>
                <participants group_id="P2" count="615"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="637"/>
                <participants group_id="P2" count="637"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="118"/>
                <participants group_id="P2" count="70"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="252"/>
                <participants group_id="P2" count="368"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Parent/Guardian</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing in Study</title>
              <participants_list>
                <participants group_id="P1" count="265"/>
                <participants group_id="P2" count="183"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Baseline Analysis Population consisted of all randomized participants who were alive at the time of randomization and had a Tumor Proportion Score (TPS) ≥1%.</population>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
        </group>
        <group group_id="B2">
          <title>Chemotherapy (SOC Treatment)</title>
          <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="637"/>
            <count group_id="B2" value="637"/>
            <count group_id="B3" value="1274"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.5" spread="9.9"/>
                    <measurement group_id="B2" value="63.1" spread="9.4"/>
                    <measurement group_id="B3" value="62.8" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="187"/>
                    <measurement group_id="B2" value="185"/>
                    <measurement group_id="B3" value="372"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="450"/>
                    <measurement group_id="B2" value="452"/>
                    <measurement group_id="B3" value="902"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                    <measurement group_id="B2" value="187"/>
                    <measurement group_id="B3" value="376"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="398"/>
                    <measurement group_id="B2" value="412"/>
                    <measurement group_id="B3" value="810"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)</title>
          <description>Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory &amp; able to carry out work of a light or sedentary nature; Grade 2: Ambulatory &amp; capable of all selfcare but unable to carry out any work activities, up &amp; about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>ECOG PS=0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="198"/>
                    <measurement group_id="B2" value="192"/>
                    <measurement group_id="B3" value="390"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG PS=1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="439"/>
                    <measurement group_id="B2" value="445"/>
                    <measurement group_id="B3" value="884"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status</title>
          <description>Participants were assessed for their PD-L1 tumor expression status by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a tumor proportion score (TPS) were classified as follows: ≥50% = PD-L1 strongly positive; 1-49% = PD-L1 weakly positive; and &lt;1% = PD-L1 negative.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>TPS=≥50%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="299"/>
                    <measurement group_id="B2" value="300"/>
                    <measurement group_id="B3" value="599"/>
                  </measurement_list>
                </category>
                <category>
                  <title>TPS=20-49%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="114"/>
                    <measurement group_id="B2" value="105"/>
                    <measurement group_id="B3" value="219"/>
                  </measurement_list>
                </category>
                <category>
                  <title>TPS=1-19%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="224"/>
                    <measurement group_id="B2" value="232"/>
                    <measurement group_id="B3" value="456"/>
                  </measurement_list>
                </category>
                <category>
                  <title>TPS=&lt;1%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumor Histology</title>
          <description>Participants were classified according to tumor histology: Squamous or Non-squamous. The tumor histology determined potential treatment regimen.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Squamous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="243"/>
                    <measurement group_id="B2" value="249"/>
                    <measurement group_id="B3" value="492"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-squamous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="394"/>
                    <measurement group_id="B2" value="388"/>
                    <measurement group_id="B3" value="782"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
        <description>OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
          <description>OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="299"/>
                <count group_id="O2" value="300"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="15.4" upper_limit="24.9"/>
                    <measurement group_id="O2" value="12.2" lower_limit="10.4" upper_limit="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0003</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.56</ci_lower_limit>
            <ci_upper_limit>0.85</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
        <description>OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
          <description>OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="413"/>
                <count group_id="O2" value="405"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.7" lower_limit="15.3" upper_limit="22.1"/>
                    <measurement group_id="O2" value="13.0" lower_limit="11.6" upper_limit="15.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0020</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.64</ci_lower_limit>
            <ci_upper_limit>0.92</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
        <description>OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
          <description>OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="637"/>
                <count group_id="O2" value="637"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.7" lower_limit="13.9" upper_limit="19.7"/>
                    <measurement group_id="O2" value="12.1" lower_limit="11.3" upper_limit="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0018</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.81</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.71</ci_lower_limit>
            <ci_upper_limit>0.93</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
        <description>PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
          <description>PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="299"/>
                <count group_id="O2" value="300"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" lower_limit="5.9" upper_limit="9.0"/>
                    <measurement group_id="O2" value="6.4" lower_limit="6.1" upper_limit="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0187</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.82</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.68</ci_lower_limit>
            <ci_upper_limit>0.99</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
        <description>PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
          <description>PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="413"/>
                <count group_id="O2" value="405"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" lower_limit="5.1" upper_limit="7.8"/>
                    <measurement group_id="O2" value="6.6" lower_limit="6.2" upper_limit="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2331</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.94</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.80</ci_lower_limit>
            <ci_upper_limit>1.11</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
        <description>PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
          <description>PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="637"/>
                <count group_id="O2" value="637"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" lower_limit="4.3" upper_limit="6.2"/>
                    <measurement group_id="O2" value="6.5" lower_limit="6.3" upper_limit="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8445</p_value>
            <p_value_desc>One-sided p-value based on stratified log-rank test</p_value_desc>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.07</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.94</ci_lower_limit>
            <ci_upper_limit>1.21</ci_upper_limit>
            <estimate_desc>Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
        <description>ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%</title>
          <description>ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="299"/>
                <count group_id="O2" value="300"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.5" lower_limit="33.9" upper_limit="45.3"/>
                    <measurement group_id="O2" value="32.0" lower_limit="26.8" upper_limit="37.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0289</p_value>
            <p_value_desc>One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages &gt;0</p_value_desc>
            <method>Stratified Miettinen and Nurminen</method>
            <param_type>Difference in Percentage (DP)</param_type>
            <param_value>7.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.2</ci_lower_limit>
            <ci_upper_limit>15.0</ci_upper_limit>
            <estimate_desc>DP for pembrolizumab vs. chemotherapy based on Miettinen &amp; Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1) and histology (squamous vs. nonsquamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
        <description>ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%</title>
          <description>ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="413"/>
                <count group_id="O2" value="405"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.4" lower_limit="28.9" upper_limit="38.2"/>
                    <measurement group_id="O2" value="28.9" lower_limit="24.5" upper_limit="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0638</p_value>
            <p_value_desc>One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages &gt;0</p_value_desc>
            <method>Stratified Miettinen and Nurminen</method>
            <param_type>Difference in Percentage (DP)</param_type>
            <param_value>4.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.4</ci_lower_limit>
            <ci_upper_limit>11.1</ci_upper_limit>
            <estimate_desc>DP for pembrolizumab vs. chemotherapy based on Miettinen &amp; Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
        <description>ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%</title>
          <description>ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.</description>
          <population>The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="637"/>
                <count group_id="O2" value="637"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.3" lower_limit="23.9" upper_limit="31.0"/>
                    <measurement group_id="O2" value="26.5" lower_limit="23.1" upper_limit="30.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3798</p_value>
            <p_value_desc>One-sided p-value for testing. H0: difference in percentages=0 vs. H1: difference in percentages &gt;0</p_value_desc>
            <method>Stratified Miettinen and Nurminen</method>
            <param_type>Difference in Percentage (DP)</param_type>
            <param_value>0.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.0</ci_lower_limit>
            <ci_upper_limit>5.5</ci_upper_limit>
            <estimate_desc>DP for pembrolizumab vs. chemotherapy based on Miettinen &amp; Nurminen method stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%) and histology (squamous vs. non-squamous).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced At Least One Adverse Event (AE)</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced At Least One Adverse Event (AE)</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="636"/>
                <count group_id="O2" value="615"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="610"/>
                    <measurement group_id="O2" value="606"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)</title>
        <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
        <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
        <population>The analysis population consisted of all participants who received ≥1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
          </group>
          <group group_id="O2">
            <title>Chemotherapy (SOC Treatment)</title>
            <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)</title>
          <description>An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date.</description>
          <population>The analysis population consisted of all participants who received ≥1 dose of study treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="636"/>
                <count group_id="O2" value="615"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122"/>
                    <measurement group_id="O2" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)</time_frame>
      <desc>Population: All participants receiving ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms &quot;Neoplasm progression&quot;, &quot;Malignant neoplasm progression&quot; &amp; &quot;Disease progression&quot; not related to study drug are excluded as AEs.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab</title>
          <description>Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)</description>
        </group>
        <group group_id="E2">
          <title>Chemotherapy (SOC Treatment)</title>
          <description>Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="370" subjects_at_risk="636"/>
                <counts group_id="E2" subjects_affected="427" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="259" subjects_at_risk="636"/>
                <counts group_id="E2" subjects_affected="187" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="24" subjects_affected="17" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Normochromic anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Splenic infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Agranulocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Bone marrow failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Aortic valve stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardiac tamponade</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cardiopulmonary failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pericarditis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypopituitarism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia of malignancy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Duodenal perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Enterocolitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastric haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastric ulcer haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastrointestinal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Glossitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Incarcerated inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Intestinal ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutropenic colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Oesophageal fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pancreatic mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Rectal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Volvulus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Accidental death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="636"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ill-defined disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Performance status decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Sudden cardiac death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hepatitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hepatitis toxic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abdominal sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Amoebiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Amoebic dysentery</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Anal abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Biliary sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of bronchiectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lung abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutropenic sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Oesophageal candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pleural infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="51" subjects_affected="47" subjects_at_risk="636"/>
                <counts group_id="E2" events="38" subjects_affected="32" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumonia klebsiella</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Post procedural cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Vascular access site infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Klebsiella infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Cervical vertebral fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Blood prolactin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Urine output decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ketoacidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Osteitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Osteoporotic fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma gastric</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Anogenital warts</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Infected neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Keratoacanthoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lung cancer metastatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Metastases to bone</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Oesophageal carcinoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of the tongue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Tumour necrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neoplasm malignant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Tumour embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered state of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cerebral ischaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Coma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Embolic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Metabolic encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Brain injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Mental disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Glomerulonephritis membranous</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Nephritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Nephropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Renal tubular necrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ovarian cyst torsion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute pulmonary oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Bronchitis chronic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Chronic respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hydrothorax</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Oesophagobronchial fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="16" subjects_affected="14" subjects_at_risk="636"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="26" subjects_affected="25" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary artery thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="636"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary fistula</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary haemorrhage</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pulmonary thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Tracheal stenosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Arterial thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Embolism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Jugular vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Peripheral artery occlusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Superior vena cava syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Venous thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypovolaemic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="636"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="636"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="527" subjects_at_risk="636"/>
                <counts group_id="E2" subjects_affected="576" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="118" subjects_affected="97" subjects_at_risk="636"/>
                <counts group_id="E2" events="317" subjects_affected="248" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="10" subjects_at_risk="636"/>
                <counts group_id="E2" events="63" subjects_affected="35" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="636"/>
                <counts group_id="E2" events="175" subjects_affected="84" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="636"/>
                <counts group_id="E2" events="82" subjects_affected="55" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="38" subjects_affected="38" subjects_at_risk="636"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="95" subjects_affected="76" subjects_at_risk="636"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="96" subjects_affected="76" subjects_at_risk="636"/>
                <counts group_id="E2" events="166" subjects_affected="130" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="90" subjects_affected="72" subjects_at_risk="636"/>
                <counts group_id="E2" events="102" subjects_affected="74" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="95" subjects_affected="71" subjects_at_risk="636"/>
                <counts group_id="E2" events="398" subjects_affected="195" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="18" subjects_affected="16" subjects_at_risk="636"/>
                <counts group_id="E2" events="40" subjects_affected="33" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="59" subjects_affected="49" subjects_at_risk="636"/>
                <counts group_id="E2" events="164" subjects_affected="106" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="90" subjects_affected="66" subjects_at_risk="636"/>
                <counts group_id="E2" events="108" subjects_affected="79" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="57" subjects_affected="52" subjects_at_risk="636"/>
                <counts group_id="E2" events="53" subjects_affected="44" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="125" subjects_affected="100" subjects_at_risk="636"/>
                <counts group_id="E2" events="186" subjects_affected="125" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="16" subjects_affected="16" subjects_at_risk="636"/>
                <counts group_id="E2" events="50" subjects_affected="33" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="32" subjects_affected="31" subjects_at_risk="636"/>
                <counts group_id="E2" events="44" subjects_affected="34" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="81" subjects_affected="63" subjects_at_risk="636"/>
                <counts group_id="E2" events="58" subjects_affected="47" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="34" subjects_affected="33" subjects_at_risk="636"/>
                <counts group_id="E2" events="27" subjects_affected="24" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="50" subjects_affected="40" subjects_at_risk="636"/>
                <counts group_id="E2" events="38" subjects_affected="31" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="82" subjects_affected="62" subjects_at_risk="636"/>
                <counts group_id="E2" events="96" subjects_affected="73" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="79" subjects_affected="60" subjects_at_risk="636"/>
                <counts group_id="E2" events="85" subjects_affected="58" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="48" subjects_affected="39" subjects_at_risk="636"/>
                <counts group_id="E2" events="35" subjects_affected="30" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="636"/>
                <counts group_id="E2" events="212" subjects_affected="87" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="636"/>
                <counts group_id="E2" events="133" subjects_affected="63" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="68" subjects_affected="64" subjects_at_risk="636"/>
                <counts group_id="E2" events="46" subjects_affected="45" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="636"/>
                <counts group_id="E2" events="213" subjects_affected="72" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="126" subjects_affected="108" subjects_at_risk="636"/>
                <counts group_id="E2" events="205" subjects_affected="131" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="62" subjects_affected="55" subjects_at_risk="636"/>
                <counts group_id="E2" events="144" subjects_affected="74" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="68" subjects_affected="61" subjects_at_risk="636"/>
                <counts group_id="E2" events="51" subjects_affected="43" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="50" subjects_affected="41" subjects_at_risk="636"/>
                <counts group_id="E2" events="33" subjects_affected="27" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="36" subjects_affected="32" subjects_at_risk="636"/>
                <counts group_id="E2" events="135" subjects_affected="70" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="34" subjects_affected="30" subjects_at_risk="636"/>
                <counts group_id="E2" events="39" subjects_affected="33" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="25" subjects_affected="23" subjects_at_risk="636"/>
                <counts group_id="E2" events="44" subjects_affected="37" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="55" subjects_affected="44" subjects_at_risk="636"/>
                <counts group_id="E2" events="61" subjects_affected="51" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="636"/>
                <counts group_id="E2" events="61" subjects_affected="52" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="636"/>
                <counts group_id="E2" events="55" subjects_affected="43" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="37" subjects_affected="33" subjects_at_risk="636"/>
                <counts group_id="E2" events="50" subjects_affected="44" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="114" subjects_affected="99" subjects_at_risk="636"/>
                <counts group_id="E2" events="71" subjects_affected="65" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="114" subjects_affected="99" subjects_at_risk="636"/>
                <counts group_id="E2" events="77" subjects_affected="68" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="57" subjects_affected="42" subjects_at_risk="636"/>
                <counts group_id="E2" events="23" subjects_affected="21" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="636"/>
                <counts group_id="E2" events="139" subjects_affected="138" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="77" subjects_affected="62" subjects_at_risk="636"/>
                <counts group_id="E2" events="19" subjects_affected="18" subjects_at_risk="615"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="77" subjects_affected="68" subjects_at_risk="636"/>
                <counts group_id="E2" events="50" subjects_affected="42" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="43" subjects_affected="37" subjects_at_risk="636"/>
                <counts group_id="E2" events="16" subjects_affected="13" subjects_at_risk="615"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme LLC</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02220894
org study id: 3475-042
secondary id: 152877
secondary id: MK-3475-042
secondary id: KEYNOTE-042
secondary id: 2014-001473-14
nct id: NCT02220894
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small
      cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to
      35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel
      or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based
      chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance
      therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that
      pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.
The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants
      enrolled in the global study, 92 were also enrolled in the China extension study for
      MK-3475-042 (NCT03850444).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.
measure: Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.
measure: Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.
measure: Number of Participants Who Experienced At Least One Adverse Event (AE)
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. These safety results are based on a 26-February-2018 data cutoff date.
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
time frame: Through Database Cutoff Date of 26-Feb-2018 (up to approximately 38 months)
description: An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. These safety results are based on a 26-February-2018 data cutoff date.
arm group label: Pembrolizumab
arm group type: Experimental
description: Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
arm group label: SOC Treatment
arm group type: Active Comparator
description: Participants receive carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m^2 IV on Day 1 of every 21-day cycle (Q3W) for a maximum of 6 cycles OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m^2 IV on Day 1 Q3W for a maximum of 6 cycles; participants with non-squamous histologies may go on to receive optional treatment with pemetrexed 500 mg/m^2 IV on Day 1 Q3W.
intervention type: Biological
intervention name: pembrolizumab
arm group label: Pembrolizumab
other name: MK-3475
other name: KEYTRUDA®
intervention type: Drug
intervention name: carboplatin
arm group label: SOC Treatment
other name: PARAPLATIN®
intervention type: Drug
intervention name: paclitaxel
arm group label: SOC Treatment
other name: TAXOL®
intervention type: Drug
intervention name: pemetrexed
arm group label: SOC Treatment
other name: ALIMTA®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Argentina
country: Brazil
country: Bulgaria
country: Canada
country: Chile
country: China
country: Colombia
country: Czech Republic
country: Estonia
country: Guatemala
country: Hong Kong
country: Hungary
country: Japan
country: Korea, Republic of
country: Latvia
country: Lithuania
country: Malaysia
country: Mexico
country: Peru
country: Philippines
country: Poland
country: Portugal
country: Romania
country: Russian Federation
country: South Africa
country: Sweden
country: Switzerland
country: Taiwan
country: Thailand
country: Turkey
country: Ukraine
country: Vietnam
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinicial Trials Information
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Pembrolizumab
mesh term: Pemetrexed
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 