***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 
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    Input: BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 .  Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer .  Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) BACKGROUND Ipilimumab is an approved treatment for patients with advanced melanoma . We aim ed to assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence . METHODS We did a double-blind , phase 3 trial in patients with stage III cutaneous melanoma ( excluding lymph node metastasis ≤1 mm or in-transit metastasis ) with adequate resection of lymph nodes ( ie , the primary cutaneous melanoma must have been completely excised with adequate surgical margins ) who had not received previous systemic therapy for melanoma from 91 hospitals located in 19 countries . Patients were r and omly assigned ( 1:1 ) , central ly by an interactive voice response system , to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses , then every 3 months for up to 3 years . Using a minimisation technique , r and omisation was stratified by disease stage and geographical region . The primary endpoint was recurrence-free survival , assessed by an independent review committee , and analysed by intention to treat . Enrollment is complete but the study is ongoing for follow-up for analysis of secondary endpoints . This trial is registered with EudraCT , number 2007 - 001974 - 10 , and Clinical Trials.gov , number NCT00636168 . FINDINGS Between July 10 , 2008 , and Aug 1 , 2011 , 951 patients were r and omly assigned to ipilimumab ( n=475 ) or placebo ( n=476 ) , all of whom were included in the intention-to-treat analyses . At a median follow-up of 2·74 years ( IQR 2·28 - 3·22 ) , there were 528 recurrence-free survival events ( 234 in the ipilimumab group vs 294 in the placebo group ) . Median recurrence-free survival was 26·1 months ( 95 % CI 19·3 - 39·3 ) in the ipilimumab group versus 17·1 months ( 95 % CI 13·4 - 21·6 ) in the placebo group ( hazard ratio 0·75 ; 95 % CI 0·64 - 0·90 ; p=0·0013 ) ; 3-year recurrence-free survival was 46·5 % ( 95 % CI 41·5 - 51·3 ) in the ipilimumab group versus 34·8 % ( 30·1 - 39·5 ) in the placebo group . The most common grade 3 - 4 immune-related adverse events in the ipilimumab group were gastrointestinal ( 75 [ 16 % ] vs four [ < 1 % ] in the placebo group ) , hepatic ( 50 [ 11 % ] vs one [ < 1 % ] ) , and endocrine ( 40 [ 8 % ] vs none ) . Adverse events led to discontinuation of treatment in 245 ( 52 % ) of 471 patients who started ipilimumab ( 182 [ 39 % ] during the initial treatment period of four doses ) . Five patients ( 1 % ) died due to drug-related adverse events . Five ( 1 % ) participants died because of drug-related adverse events in the ipilimumab group ; three patients died because of colitis ( two with gastrointestinal perforation ) , one patient because of myocarditis , and one patient because of multiorgan failure with Guillain-Barré syndrome . INTERPRETATION Adjuvant ipilimumab significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma . The adverse event profile was consistent with that observed in advanced melanoma , but at higher incidences in particular for endocrinopathies . The risk-benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value . FUNDING Bristol-Myers Squibb 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 This phase II study evaluated the safety and activity of ipilimumab , a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4 , in patients with advanced melanoma . PATIENTS AND METHODS Patients with previously treated , unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles ( induction ) followed by maintenance therapy every 3 months . The primary end point was best overall response rate ( BORR ) using modified World Health Organization ( WHO ) criteria . We also carried out an exploratory analysis of proposed immune-related response criteria ( irRC ) . RESULTS BORR was 5.8 % with a disease control rate ( DCR ) of 27 % ( N = 155 ) . One- and 2-year survival rates ( 95 % confidence interval ) were 47.2 % ( 39.5 % to 55.1 % ) and 32.8 % ( 25.4 % to 40.5 % ) , respectively , with a median overall survival of 10.2 months ( 7.6 - 16.3 ) . Of 43 patients with disease progression by modified WHO criteria , 12 had disease control by irRC ( 8 % of all treated patients ) , result ing in a total DCR of 35 % . Adverse events ( AEs ) were largely immune related , occurring mainly in the skin and gastrointestinal tract , with 19 % grade 3 and 3.2 % grade 4 . Immune-related AEs were manageable and generally reversible with corticosteroids . CONCLUSION Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population BACKGROUND Ipilimumab , an anti-CTLA4 monoclonal antibody , demonstrated survival benefit in melanoma with immune-related ( ir ) adverse events ( irAEs ) managed by the protocol -defined guidelines . This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer ( ED-SCLC ) . DESIGN Patients ( n=130 ) with chemotherapy-naïve ED-SCLC were r and omized 1 : 1 : 1 to receive paclitaxel ( 175 mg/m2)/carboplatin ( area under the curve=6 ) with either placebo ( control ) or ipilimumab 10 mg/kg in two alternative regimens , concurrent ipilimumab ( ipilimumab+paclitaxel/carboplatin 
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Conclusion The cytotoxic T-lymphocyte-associated protein-4 ( CTLA-4 ) inhibitors have a significantly higher risk of FAE ( P=0.01 ) , whereas programmed cell death protein 1 ( PD-1 ) inhibitors were not .
The most common CTLA-4-related FAE was gastrointestinal toxicity , and the most common PD-1-related FAE was pulmonary toxicity .
Moreover , we have shown that ipilimumab has significant dose-dependent lethal toxicity