***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 Nivolumab ( a programmed death 1 [ PD-1 ] checkpoint inhibitor ) and ipilimumab ( a cytotoxic T-lymphocyte-associated antigen 4 [ CTLA-4 ] checkpoint inhibitor ) have been shown to have complementary activity in metastatic melanoma . In this r and omized , double-blind , phase 3 study , nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma . METHODS We assigned , in a 1:1:1 ratio , 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone , nivolumab plus ipilimumab , or ipilimumab alone  . Progression-free survival and overall survival were co primary end points . Results regarding progression-free survival are presented here . RESULTS The median progression-free survival was 11.5 months ( 95 % confidence interval [ CI ] , 8.9 to 16.7 ) with nivolumab plus ipilimumab , as compared with 2.9 months ( 95 % CI , 2.8 to 3.4 ) with ipilimumab ( hazard ratio for death or disease progression , 0.42 ; 99.5 % CI , 0.31 to 0.57 ; P<0.001 ) , and 6.9 months ( 95 % CI , 4.3 to 9.5 ) with nivolumab ( hazard ratio for the comparison with ipilimumab , 0.57 ; 99.5 % CI , 0.43 to 0.76 ; P<0.001 ) . In patients with tumors positive for the PD-1 lig and ( PD-L1 ) , the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group , but in patients with PD-L1-negative tumors , progression-free survival was longer with the combination therapy than with nivolumab alone ( 11.2 months [ 95 % CI , 8.0 to not reached ] vs. 5.3 months [ 95 % CI , 2.8 to 7.1 ] ) . Treatment-related adverse events of grade 3 or 4 occurred in 16.3 % of the patients in the nivolumab group , 55.0 % of those in the nivolumab-plus-ipilimumab group , and 27.3 % of those in the ipilimumab group . CONCLUSIONS Among previously untreated patients with metastatic melanoma , nivolumab alone or combined with ipilimumab result ed in significantly longer progression-free survival than ipilimumab alone . In patients with PD-L1-negative tumors , the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone . ( Funded by Bristol-Myers Squibb ; CheckMate 067 Clinical Trials.gov number , NCT01844505 . ) 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 PURPOSE Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors . We report clinical activity , survival , and long-term safety in patients with advanced renal cell carcinoma ( RCC ) treated with nivolumab in a phase I study with expansion cohorts . PATIENTS AND METHODS A total of 34 patients with previously treated advanced RCC , enrolled between 2008 and 2012 , received intravenous nivolumab ( 1 or 10 mg/kg ) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation . RESULTS Ten patients ( 29 % ) achieved objective responses ( according to RECIST [ version 1.0 ] ) , with median response duration of 12.9 months ; nine additional patients ( 27 % ) demonstrated stable disease lasting > 24 weeks . Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks . Median overall survival in all patients ( 71 % with two to five prior systemic therapies ) was 22.4 months ; 1- , 2- , and 3-year survival rates were 71 % , 48 % , and 44 % , respectively . Grade 3 to 4 treatment-related adverse events occurred in 18 % of patients ; all were reversible . CONCLUSION Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation . Overall survival is encouraging , and toxicities were generally manageable . Ongoing r and omized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC BACKGROUND The immune checkpoint inhibitor ipilimumab is the st and ard-of-care treatment for patients with advanced melanoma .  Pembrolizumab inhibits the programmed cell death 1 ( PD-1 ) immune checkpoint and has antitumor activity in patients with advanced melanoma . METHODS In this r and omized , controlled , phase 3 study , we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab ( at a dose of 10 mg per kilogram of body weight ) every 2 weeks or every 3 weeks or four doses of ipilimumab ( at 3 mg per kilogram ) every 3 weeks . Primary end points were progression-free and overall survival . RESULTS The estimated 6-month progression-free-survival rates were 47.3 % for pembrolizumab every 2 weeks , 46.4 % for pembrolizumab every 3 weeks , and 26.5 % for ipilimumab ( hazard ratio for disease progression , 0.58 ; P<0.001 for both pembrolizumab regimens versus ipilimumab ; 95 % confidence intervals [ CIs ] , 0.46 to 0.72 and 0.47 to 0.72 , respectively ) . Estimated 12-month survival rates were 74.1 % , 68.4 % , and 58.2 % , respectively ( hazard ratio for death for pembrolizumab every 2 weeks , 0.63 ; 95 % CI , 0.47 to 0.83 ; P=0.0005 ; hazard ratio for pembrolizumab every 3 weeks , 0.69 ; 95 % CI , 0.52 to 0.90 ; P=0.0036 ) . The response rate was improved with pembrolizumab administered every 2 weeks ( 33.7 % ) and every 3 weeks ( 32.9 % ) , as compared with ipilimumab ( 11.9 % ) ( P<0.001 for both comparisons ) . Responses were ongoing in 89.4 % , 96.7 % , and 87.9 % of patients , respectively , after a median follow-up of 7.9 months . Efficacy was similar in the two pembrolizumab groups . Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups ( 13.3 % and 10.1 % ) than in the ipilimumab group ( 19.9 % ) . CONCLUSIONS The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high- grade toxicity than did ipilimumab in patients with advanced melanoma . ( Funded by Merck Sharp & Dohme ; KEYNOTE-006 Clinical Trials.gov number , NCT01866319 . ) 
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These significance s were reflected in the subgroup of melanoma metastases .
Conclusion Based on the trends of our findings , there appears to exist an optimal time window around SRS of which ICI may confer the most survival benefit .