***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: 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 & Background Pembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death lig and 1 ( PD-L1 ) expressing advanced non-small cell lung cancer ( NSCLC ) . We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy . Patients and methods In the open-label phase 1b KEYNOTE-001 trial , treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 ( ≥1 % staining , assessed using a prototype assay ) were r and omly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 ( Q3W ) or 2 ( Q2W ) weeks . Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received ≥1 pembrolizumab dose . Using pre-treatment tumor tissue , a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score ( TPS ) . Results Between 1 March 2013 and 18 September 2015 , 101 patients received pembrolizumab 2 mg/kg Q3W ( n = 6 ) , 10 mg/kg Q3W ( n = 49 ) , or 10 mg/kg Q2W ( n = 46 ) . Of these , 27 ( 26.7 % ) had TPS ≥50 % , 52 ( 51.5 % ) had TPS 1%–49 % , and 12 ( 11.9 % ) had TPS < 1 % . The objective response rate ( ORR ) was 27 % ( 27/101 , 95 % CI 18–37 ) and median overall survival was 22.1 months ( 95 % CI 17.1–27.2 ) . In patients with PD-L1 TPS ≥50 % , ORR , 12-month PFS , and 12-month OS were higher [ 14/27 ( 51.9 % ; 95 % CI 32%–71 % ) , 54 % , and 85 % , respectively ] than the overall population [ 27/101 ( 26.7 % ; 95 % CI 18.4%–36.5 % ) , 35 % , 71 % ] . Pembrolizumab was well tolerated , with only 12 ( 11.9 % ) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths . Conclusions Pembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC , with greatest efficacy observed in patients with TPS ≥50 % . Clinical trial name and number KEYNOTE-001 ( Clinical Trials.gov , NCT01295827 ) BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy .  Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P<0.001 ) . The estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . ) PURPOSE Nivolumab , a programmed death-1 ( PD-1 ) immune checkpoint inhibitor antibody , has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer ( NSCLC ) . First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I , multicohort , Checkmate 012 trial . METHODS Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity ; postprogression treatment was permitted per protocol . The primary objective was to assess safety ; secondary objectives included objective response rate ( ORR ) and 24-week progression-free survival ( PFS ) rate ; overall survival ( OS ) was an exploratory end point . RESULTS Any- grade treatment-related adverse events ( AEs ) occurred in 71 % of patients , most commonly : fatigue ( 29 % ) , rash ( 19 % ) , nausea ( 14 % ) , diarrhea ( 12 % ) , pruritus ( 12 % ) , and arthralgia ( 10 % ) . Ten patients ( 19 % ) reported grade 3 to 4 treatment-related AEs ; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient ( n = 2 ; 4 % ) . Six patients ( 12 % ) discontinued because of a treatment-related AE . The confirmed ORR was 23 % ( 12 of 52 ) , including four ongoing complete responses . Nine of 12 responses ( 75 % ) occurred by first tumor assessment ( week 11 ) ; eight ( 67 % ) were ongoing ( range , 5.3 + to 25.8 + months ) at the time of data lock . ORR was 28 % ( nine of 32 ) in patients with any degree of tumor PD-lig and 1 expression and 14 % ( two of 14 ) in patients with no PD-lig and 1 expression . Median PFS was 3.6 months , and the 24-week PFS rate was 41 % ( 95 % CI , 27 to 54 ) . Median OS was 19.4 months , and the 1-year and 18-month OS rates were 73 % ( 95 % CI , 59 to 83 ) and 57 % ( 95 % CI , 42 to 70 ) , respectively . CONCLUSION First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC ABSTRACT Patients with EGFR mutations showed unfavorable response to programmed cell death-1 ( PD-1 ) blockade immunotherapy in non-small cell lung cancer ( NSCLC ) . Yet the underlying association between EGFR mutation and immune resistance remains largely unclear . We performed an integrated analysis of PD-lig and 1(PD-L1)/CD8 expression and mutation profile based on the repository data base and resected early-stage NSCLC in Guangdong Lung Cancer Institute ( GLCI ) . Meanwhile , 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression , and the association of EGFR status with response to anti-PD-1/L1 therapy . Pool- analysis of 15 public studies suggested that patients with EGFR mutations had decreased PD-L1 expression ( odds ratio : 1.79 , 95 % CI : 1.10– 
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Conclusions PD-1/PD-L1 inhibitor plus chemotherapy , compared with chemotherapy , is associated with significantly improved PFS , ORR , and OS in first-line therapy in NSCLC , at the expense of increased treatment-related AEs