***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 Treatments for small-cell lung cancer ( SCLC ) after failure of platinum-based chemotherapy are limited . We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens . METHODS The SCLC cohort of this phase 1/2 multicentre , multi-arm , open-label trial was conducted at 23 sites ( academic centres and hospitals ) in six countries . Eligible patients were 18 years of age or older , had limited-stage or extensive-stage SCLC , and had disease progression after at least one previous platinum-containing regimen . Patients received nivolumab ( 3 mg/kg bodyweight intravenously ) every 2 weeks ( given until disease progression or unacceptable toxicity ) , or nivolumab plus ipilimumab ( 1 mg/kg plus 1 mg/kg , 1 mg/kg plus 3 mg/kg , or 3 mg/kg plus 1 mg/kg , intravenously ) every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks . Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg . Depending on tolerability , patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . The primary endpoint was objective response by investigator assessment . All analyses included patients who were enrolled at least 90 days before data base lock . This trial is ongoing ; here , we report an interim analysis of the SCLC cohort . This study is registered with Clinical Trials.gov , number NCT01928394 . FINDINGS Between Nov 18 , 2013 , and July 28 , 2015 , 216 patients were enrolled and treated ( 98 with nivolumab 3 mg/kg , three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg ) . At data base lock on Nov 6 , 2015 , median follow-up for patients continuing in the study ( including those who had died or discontinued treatment ) was 198·5 days ( IQR 163·0 - 464·0 ) for nivolumab 3 mg/kg , 302 days ( IQR not calculable ) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 361·0 days ( 273·0 - 470·0 ) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 260·5 days ( 248·0 - 288·0 ) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . An objective response was achieved in ten ( 10 % ) of 98 patients  receiving nivolumab 3 mg/kg , one ( 33 % ) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 14 ( 23 % ) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and ten ( 19 % ) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . Grade 3 or 4 treatment-related adverse events occurred in 13 ( 13 % ) patients in the nivolumab 3 mg/kg cohort , 18 ( 30 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort , and ten ( 19 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( none vs 5 [ 8 % ] vs none ) and diarrhoea ( none vs 3 [ 5 % ] vs 1 [ 2 % ] ) . No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event . Six ( 6 % ) patients in the nivolumab 3 mg/kg group , seven ( 11 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group , and four ( 7 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events . Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events ( myasthenia gravis and worsening of renal failure ) , and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis . INTERPRETATION Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC . These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 r and omised controlled trials in SCLC . FUNDING Bristol-Myers Squibb 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 Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab ( an anti-PD-1 antibody ) plus ipilimumab ( an anti-CTLA-4 antibody ) compared with ipilimumab alone . We report 2-year overall survival data from a r and omised controlled trial assessing this treatment in previously untreated advanced melanoma . METHODS In this multicentre , double-blind , r and omised , controlled , phase 2 trial ( CheckMate 069 ) we recruited patients from 19 specialist cancer centres in two countries ( France and the USA ) . Eligible patients were aged 18 years or older with previously untreated , unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients were r and omly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo , every 3 weeks for four doses . Subsequently , patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity , whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase . R and omisation was done via an interactive voice response system with a permuted block schedule ( block size of six ) and stratification by BRAF mutation status . The study funder , patients , investigators , and study site staff were masked to treatment assignment . The primary endpoint , which has been reported previously , was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response . Overall survival was an exploratory endpoint and is reported in this Article . Efficacy analyses were done on the intention-to-treat population , whereas safety was assessed in all treated patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01927419 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 16 , 2013 , and Feb 6 , 2014 , we screened 179 patients and enrolled 142 , r and omly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone . In each treatment group , one patient no longer met the study criteria following r and omisation and thus did not receive study drug . At a median follow-up of 24·5 months ( IQR 9·1 - 25·7 ) , 2-year overall survival was 63·8 % ( 95 % CI 53·3 - 72·6 ) for those assigned to nivolumab plus ipilimumab and 53·6 % ( 95 % CI 38·1 - 66·8 ) for those assigned to ipilimumab alone ; median overall survival had not been reached in either group ( hazard ratio 0·74 , 95 % CI 0·43 - 1·26 ; p=0·26 ) . Treatment-related grade 3 - 4 adverse events were reported in 51 ( 54 % ) of 94 patients who received nivolumab plus ipilimumab compared with nine ( 20 % ) of 46 patients who received ipilimumab alone . The most common treatment-related grade 3 - 4 adverse events were colitis ( 12 [ 13 % ] of 94 patients ) and increased alanine aminotransferase ( ten [ 11 % ] ) in the combination group and diarrhoea ( five [ 11 % ] of 46 patients ) and hypophysitis ( two [ 4 % ] ) in the ipilimumab alone 
    Output:
    
There was no significant difference in any grade pneumonitis and pneumonia in cytotoxic T lymphocyte-associated protein 4 ( CTLA4 ) inhibitors subgroup .
Conclusions : PD-1/PD-L1 inhibitors treatment could increase the risk of all- grade pneumonitis .
CTLA4  inhibitor ipilimumab treatment alone could not increase the risk of pneumonitis but could augment the risk of pneumonitis in PD-1/PD-L1 inhibitor treated patients .
There was no significant increase in the risk of pneumonia after either PD-1/PDL-1inhibitor or CTLA4 inhibitor treatment alone or in combination