***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: AIM To evaluate the protocol -specified final analysis of overall survival ( OS ) in the KEYNOTE-002 study ( NCT01704287 ) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory , advanced melanoma . METHODS In this r and omised , phase II study , eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses , previous BRAF or MEK inhibitor or both , if BRAFV600 mutant-positive . Patients were r and omised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or  investigator-choice chemotherapy . Crossover to pembrolizumab was allowed following progression on chemotherapy . The protocol -specified final OS was performed in the intent-to-treat population . Survival was positive if p < 0.01 in one pembrolizumab arm . RESULTS A total of 180 patients were r and omised to pembrolizumab 2 mg/kg , 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy . At a median follow-up of 28 months ( range 24.1 - 35.5 ) , 368 patients died and 98 ( 55 % ) crossed over to pembrolizumab . Pembrolizumab 2 mg/kg ( hazard ratio [ HR ] 0.86 , 95 % confidence interval [ CI ] 0.67 - 1.10 , p = 0.117 ) and 10 mg/kg ( 0.74 , 0.57 - 0.96 , p = 0.011 ) result ed in a non-statistically significant improvement in OS versus chemotherapy ; median OS was 13.4 ( 95 % CI 11.0 - 16.4 ) and 14.7 ( 95 % CI 11.3 - 19.5 ) , respectively , versus 11.0 months ( 95 % CI 8.9 - 13.8 ) , with limited improvement after censoring for crossover . Two-year survival rates were 36 % and 38 % , versus 30 % . Progression-free survival , objective response rate and duration of response improved with pembrolizumab versus chemotherapy , regardless of dose . Grade III-V treatment-related adverse events occurred in 24 ( 13.5 % ) , 30 ( 16.8 % ) and 45 ( 26.3 % ) patients , respectively . CONCLUSION Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy 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 Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to  receive  docetaxel  .  Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , Background The programmed death 1 ( PD‐1 ) inhibitor pembrolizumab has been found to prolong progression‐free and overall survival among patients with advanced melanoma . We conducted a phase 3 double‐blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected , high‐risk stage III melanoma . Methods Patients with completely resected stage III melanoma were r and omly assigned ( with stratification according to cancer stage and geographic region ) to receive 200 mg of pembrolizumab ( 514 patients ) or placebo ( 505 patients ) intravenously every 3 weeks for a total of 18 doses ( approximately 1 year ) or until disease recurrence or unacceptable toxic effects occurred . Recurrence‐free survival in the overall intention‐to‐treat population and in the subgroup of patients with cancer that was positive for the PD‐1 lig and ( PD‐L1 ) were the primary end points . Safety was also evaluated . Results At a median follow‐up of 15 months , pembrolizumab was associated with significantly longer recurrence‐free survival  than placebo in the overall intention‐to‐treat population ( 1‐year rate of recurrence‐free survival , 75.4 % [ 95 % confidence interval { CI } , 71.3 to 78.9 ] vs. 61.0 % [ 95 % CI , 56.5 to 65.1 ] ; hazard ratio for recurrence or death , 0.57 ; 98.4 % CI , 0.43 to  
    Output:
    
Compared with PD-L1 inhibitors , PD-1 inhibitors neither increased trAEs nor irAEs significantly .
Conclusions : Current data showed that PD-L1 inhibitors had the best safety on both trAEs and irAEs .