***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: A companion diagnostic assay was codeveloped by Dako for pembrolizumab non – small-cell lung cancer clinical trials to detect PD-L1 expression by immunohistochemistry ( IHC ) . This automated IHC assay has been analytically verified and vali date d using Dako ’s autostainer Link 48 and 22C3 mouse anti-PD-L1 monoclonal antibody to detect the PD-L1 expression in formalin-fixed paraffin-embedded human tumor tissue specimens . The PD-L1 22C3 IHC assay was optimized for high sensitivity and specificity . Repeatability and reproducibility studies were conducted at Dako and at 3 Clinical Laboratory Improvement Amendments certified laboratories during assay development . The studies included : intersite and intrasite , interobserver and intraobserver , interinstrument , interoperator , interday , and interlot , and intraday and intrarun . All precision studies performed at Dako and external laboratories achieved > 85 % point-estimate agreements for all 3 agreement types ( negative , positive , and overall ) . A clinical cutoff ( tumor proportion score ≥50 % ) of PD-L1 expression was determined and evaluated through a phase 1 clinical trial ( KEYNOTE-001 ) for advanced non – small-cell lung cancer patients treated with pembrolizumab . The treatment effect of pembrolizumab in the 61 subjects who had a tumor PD-L1 of tumor proportion score ≥50 % was substantial , with an overall response rate of 41 % ( 95 % confidence interval , 28.6 - 54.3 ) as compared with 20.6 % ( 95 % confidence interval , 15.5 - 26.5 ) observed in the 223 subjects irrespective of PD-L1 status . PD-L1 IHC 22C3 pharmDx is a sensitive , precise , and robust companion diagnostic assay , which will facilitate safe and effective use for pembrolizumab in cancer patients BACKGROUND In the phase 3 KEYNOTE-024 trial , treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive , advanced non-small-cell lung cancer ( NSCLC ) with a programmed cell death-lig and 1 ( PD-L1 ) tumour proportion score of 50 % or greater ( PD-L1-positive ) . Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes ( PROs ) . METHODS In this multicentre , international , r and omised , open-label , phase 3 trial , we recruited patients with treatment-naive , stage IV NSCLC in 102 sites in 16 countries . Eligible patients had measurable disease ( per RECIST version 1.1 ) and an Eastern Cooperative Oncology Group ( ECOG ) performance status 0 or 1 . Patients were r and omly assigned ( 1:1 ) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks ( 35 cycles ) or investigator-choice platinum-doublet chemotherapy ( 4 - 6 cycles or until documented disease progression or unacceptable toxicity ) . R and omisation was stratified according to geography , ECOG performance status , and histology . PROs were assessed at day 1 of cycles 1 - 3 , every 9 weeks thereafter , at the treatment discontinuation visit , and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire Core 30 items ( QLQ-C30 ) , the EORTC Quality of Life Question naire Lung Cancer 13 items ( QLQ-LC13 ) , and the European Quality of Life 5 Dimensions-3 Level ( EQ-5D-3L ) question naire . The key exploratory PRO endpoints ( analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint ) were baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/ quality -of-life ( QOL ) score and time to deterioration of the composite of cough , chest pain , and dyspnoea in the QLQ-LC13 . This study is registered with Clinical Trials.gov , number NCT02142738 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 19 , 2014 , and Oct 29 , 2015 , 305 patients were r and omly assigned to pembrolizumab ( n=154 ) or chemotherapy ( n=151 ) . Three patients in each group did not complete any PRO instruments at any timepoints , and so 299 patients were included in the full analysis set . Of these patients , one in each group did not complete any PRO instruments before week 15 , and so were not included in analyses of change from baseline to week 15 . PRO compliance was greater than 90 % at baseline and approximately 80 % at week 15 for both groups . Least-squares mean baseline-to-week-15 change in QLQ-C30 GHS/QOL score was 6·9 ( 95 % CI 3·3 to 10·6 ) for pembrolizumab and -0·9 ( -4·8 to 3·0 ) for chemotherapy , for a difference of 7·8 ( 2·9 to 12·8 ; two-sided nominal p=0·0020 ) . Fewer pembrolizumab-treated patients had deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients ( 46 [ 31 % ] of 151 patients vs 58 [ 39 % ] of 148 patients ) . Time to deterioration was longer with pembrolizumab than with chemotherapy ( median not reached [ 95 % CI 8·5 to not reached ] vs 5·0 months [ 3·6 to not reached ] ; hazard ratio 0·66 , 95 % CI 0·44 - 0·97 ; two-sided nominal p=0·029 ) . INTERPRETATION Pembrolizumab improves or maintains health-related QOL compared with that for chemotherapy , and might represent a new first-line st and ard of care for PD-L1-expressing , advanced NSCLC . FUNDING Merck & BACKGROUND Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & Purpose Patients with squamous non-small-cell lung cancer ( NSCLC ) have poor prognosis and limited treatment options . This r and omized , double-blind , phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC . Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were r and omly assigned ( 1:1 ) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles , with ipilimumab or placebo from cycles 3 to 6 and then , after induction treatment , ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better . The primary end point was overall survival ( OS ) in patients receiving at least one dose of blinded study therapy . Results Of 956 r and omly assigned patients , 749 received at least one dose of blinded study therapy  ( chemotherapy plus ipilimumab , n = 388 ; chemotherapy plus placebo , n = 361 ) . Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo ( hazard ratio , 0.91 ; 95 % CI , 0.77 to 1.07 ; P = .25 ) . Median progression-free survival was 5.6 months for both groups ( hazard ratio , 0.87 ; 95 % CI , 0.75 to 1.01 ) . Rates of grade 3 or 4 treatment-related adverse events ( TRAEs ) , any- grade serious TRAEs , and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab ( 51 % , 33 % , and 28 % , respectively ) than with chemotherapy plus placebo ( 35 % , 10 % , and 7 % , respectively ) . Seven treatment-related deaths occurred with chemotherapy plus ipilimumab , and one occurred with chemotherapy plus placebo . Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC . The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies . Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy 
    Output:
    
Immunotherapy plus chemotherapy appeared superior to Pembrolizumab alone for PD-L1-high ( i.e. , TPS≥50 % ) NSCLC patients .
BC might also be specifically recommended as an initial first-line treatment for PD-L1-high , non-squamous NSCLC patients , since BC was not inferior to Pembrolizumab alone .
PC and ABC might be preferred for NSCLC patients with intermediate PD-L1 ( 1 % ≤PD-L1 , TPS<50 % ) expression .
BC can also be tentatively recommended specifically for PD-L1-intermediate , non-squamous NSCLC patients .
Combined immunotherapies can all be recommended for PD-L1-negative ( i.e. , TPS<1 % ) NSCLC patients , although especially the ABC combination for non-squamous NSCLC patients , which was superior to PC in regards of PFS .
However , PC performed comparable to ABC in the whole population and in all subgroup save this one .