***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 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 Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND Cabozantinib is an oral inhibitor of tyrosine kinases including MET , VEGFR , and AXL . The r and omised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment . Here , we report the final overall survival results from this study based on an unplanned second interim analysis . METHODS In this open-label , r and omised phase 3 trial , we r and omly assigned ( 1:1 ) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma , measurable disease , and previous treatment with one or more VEGFR tyrosine-kinase inhibitors  to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day . R and omisation was done with an interactive voice and web response system . Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors . The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 r and omly assigned patients and has been previously reported . Secondary endpoints were overall survival and objective response in all r and omly assigned patients assessed by intention-to-treat . Safety was assessed per protocol in all patients who received at least one dose of study drug . The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation . This trial is registered with Clinical Trials.gov , number NCT01865747 . FINDINGS Between Aug 8 , 2013 , and Nov 24 , 2014 , 658 patients were r and omly assigned to receive cabozantinib ( n=330 ) or everolimus ( n=328 ) . The median duration of follow-up for overall survival and safety was 18·7 months ( IQR 16·1 - 21·1 ) in the cabozantinib group and 18·8 months ( 16·0 - 21·2 ) in the everolimus  group . Median overall survival was 21·4 months ( 95 % CI 18·7-not estimable ) with cabozantinib and 16·5 months ( 14·7 - 18·8 ) with everolimus ( hazard ratio [ HR ] 0·66 [ 95 % CI 0·53 - 0·83 ] ; p=0·00026 ) . Cabozantinib treatment also result ed in improved progression-free survival ( HR 0·51 [ 95 % CI 0·41 - 0·62 ] ; p<0·0001 ) and objective response ( 17 % [ 13 - 22 ] with cabozantinib vs 3 % [ 2 - 6 ] with everolimus ; p<0·0001 ) per independent radiology review among all r and omised patients . The most common grade 3 or 4 adverse events were hypertension ( 49 [ 15 % ] in the cabozantinib group vs 12 [ 4 % ] in the everolimus group ) , diarrhoea ( 43 [ 13 % ] vs 7 [ 2 % ] ) , fatigue ( 36 [ 11 % ] vs 24 [ 7 % ] ) , palmar-plantar erythrodysaesthesia syndrome ( 27 [ 8 % ] vs 3 [ 1 % ] ) , anaemia ( 19 [ 6 % ] vs 53 [ 17 % ] ) , hyperglycaemia ( 3 [ 1 % ] vs 16 [ 5 % ] ) , and hypomagnesaemia ( 16 [ 5 % ] vs none ) . Serious adverse events grade 3 or worse occurred in 130 ( 39 % ) patients in the cabozantinib group and in 129 ( 40 % ) in the everolimus group . One treatment-related death occurred in the cabozantinib group ( death ; not otherwise specified ) and two occurred in the everolimus group ( one aspergillus infection and one pneumonia aspiration ) . INTERPRETATION Treatment with cabozantinib  increased overall survival , delayed disease progression , and improved the objective response compared with everolimus . Based on these results , cabozantinib should be considered as a new st and ard-of-care treatment option for previously treated patients with advanced renal cell carcinoma . Patients should be monitored for adverse events that might require dose modifications . FUNDING Exelixis BACKGROUND In the phase 3 CheckMate 025 study , previously treated patients with advanced renal cell carcinoma who were r and omly assigned to nivolumab  had an overall survival benefit compared with those assigned to everolimus . We aim ed to compare health-related quality of life ( HRQoL ) between treatment groups in this trial . METHODS CheckMate 025 was an open-label study done at 146 oncology centres in 24 countries . Patients were r and omly assigned to treatment between Oct 22 , 2012 , and March 11 , 2014 . Patients with advanced renal cell carcinoma were r and omly assigned ( 1:1 , block size of four ) to receive nivolumab every 2 weeks or everolimus once per day . The study was stopped early at the planned interim analysis in July , 2015 , because the study met its primary endpoint . A protocol amendment permitted patients in the everolimus group to cross over to nivolumab treatment . All patients not on active study therapy are being followed up for survival . At the interim analysis , HRQoL was assessed with the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease Related Symptoms ( FKSI-DRS ) and European Quality of Life (EuroQol)-5 Dimensions ( EQ-5D ) question naires . Prespecified endpoints were to assess , in each treatment group , disease-related symptom progression rate based on the FKSI-DRS and changes in reported global health outcomes based on the EQ-5D . Other endpoints were post hoc . We calculated the proportion of FKSI-DRS question naires completed using the number of patients with non-missing data at baseline and at least one post-baseline visit . We defined FKSI-DRS completion as completion of five or more of the nine items in the question naire ; otherwise data were treated as missing . FKSI-DRS symptom index score was prorated for missing items . We made no adjustments for missing EQ-5D data . We used descriptive statistics and multivariate analyses , including mixed-effects model repeated- measures , for between group comparisons . Analyses were powered according to the original study protocol , and we analysed FKSI-DRS and EQ-5D data for all patients who underwent r and omisation and had a baseline assessment and at least one post-baseline assessment . CheckMate 025 is registered with Clinical Trials.gov , number NCT01668784 . FINDINGS HRQoL data were collected at baseline for 362 ( 88 % ) of 410 patients in the nivolumab group and 344 ( 84 % ) of 411 patients in the everolimus group . The mean difference in FKSI-DRS scores between the nivolumab and everolimus groups was 1·6 ( 95 % CI 1·4 - 1·9 ; p<0·0001 ) with descriptive statistics and 1·7 ( 1·2 - 2·1 ; p<0·0001 ) with mixed-effects model repeated- measures analysis . In terms of FKSI-DRS score , more patients had a clinical ly meaningful ( ie , an increase of at least 2 points from baseline ) HRQoL improvement with nivolumab ( 200 [ 55 % ] of 361 patients ) versus everolimus ( 126 [ 37 % ] of 343 patients ; p<0·0001 ) . Median time to HRQoL improvement was shorter in patients given nivolumab ( 4·7 months , 95 % CI 3·7 - 7·5 ) than 
    Output:
    
In UCC and RCC , there was no conclusive association between programmed cell death receptor lig and 1 ( PD-L1 ) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment , respectively .
In metastatic UCC and RCC , pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus , respectively .
No beneficial effect of ipilimumab was observed in prostate cancer patients .
PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome .
In second-line setting , pembrolizumab and nivolumab are safe and confer survival benefit in advanced urothelial cell and renal cell cancer , respectively