***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: Therapies that target the programmed death-1 ( PD-1 ) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types . One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 lig and ( PD-L1 ) and its ligation to PD-1 on antigen-specific CD8 + T cells ( termed adaptive immune resistance ) . Here we show that pre-existing CD8 + T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy . We analysed sample s from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy ( pembrolizumab )  using quantitative immunohistochemistry , quantitative multiplex immunofluorescence , and next-generation sequencing for T-cell antigen receptors ( TCRs ) . In serially sample d tumours , patients responding to treatment showed proliferation of intratumoral CD8 + T cells that directly correlated with radiographic reduction in tumour size . Pre-treatment sample s obtained from responding patients showed higher numbers of CD8- , PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours , with close proximity between PD-1 and PD-L1 , and a more clonal TCR repertoire . Using multivariate analysis , we established a predictive model based on CD8 expression at the invasive margin and vali date d the model in an independent cohort of 15 patients . Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 + T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy  to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel .  The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the  nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy  than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy  , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) BACKGROUND Nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors . We assessed the efficacy and safety of nivolumab compared with investigator 's choice of chemotherapy ( ICC ) as a second-line or later-line treatment in patients with advanced melanoma . METHODS In this r and omised , controlled , open-label , phase 3 trial , we recruited patients at 90 sites in 14 countries . Eligible patients were 18 years or older , had unresectable or metastatic melanoma , and progressed after ipilimumab , or ipilimumab and a BRAF inhibitor if they were BRAF(V 600 ) mutation-positive . Participating investigators r and omly assigned ( with an interactive voice response system ) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC ( dacarbazine 1000 mg/m(2 ) every 3 weeks or paclitaxel 175 mg/m(2 ) combined with carboplatin area under the curve 6 every 3 weeks ) until progression or unacceptable toxic effects . We stratified r and omisation by BRAF mutation status , tumour expression of PD-L1 , and previous best overall response to ipilimumab . We used permuted blocks ( block size of six ) within each stratum . Primary endpoints were the proportion of patients who had an objective response and overall survival . Treatment was given open-label , but those doing tumour assessment s were masked to treatment assignment . We assessed objective responses per- protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks , and safety in all patients who had had at least one dose of treatment . The trial is closed and this is the first interim analysis , reporting the objective response primary endpoint . This study is registered with Clinical Trials.gov , number NCT01721746 . FINDINGS Between Dec 21 , 2012 , and Jan 10 , 2014 , we screened 631 patients , r and omly allocating 272 patients to nivolumab and 133 to ICC . Confirmed objective responses were reported in 38 ( 31·7 % , 95 % CI 23·5 - 40·8 ) of the first 120 patients in the nivolumab group versus five ( 10·6 % , 3·5 - 23·1 ) of 47 patients in the ICC group . Grade 3 - 4 adverse events related to nivolumab included increased lipase ( three [ 1 % ] of 268 patients ) , increased alanine aminotransferase , anaemia , and fatigue ( two [ 1 % ] each ) ; for ICC , these included neutropenia ( 14 [ 14 % ] of 102 ) , thrombocytopenia ( six [ 6 % ] ) , and anaemia ( five [ 5 % ] ) . We noted grade 3 - 4 drug-related serious adverse events in 12 ( 5 % ) nivolumab-treated patients and nine ( 9 % ) patients in the ICC group . No treatment-related deaths occurred . INTERPRETATION Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor . Nivolumab represents a new treatment option with clinical ly meaningful durable objective responses in a population of high unmet need . FUNDING Bristol-Myers Squibb BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer ( NSCLC ) who have disease progression during or after first-line chemotherapy have limited treatment options . This r and omized , open-label , international , phase 3 study evaluated the efficacy and safety of nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , as compared with docetaxel in this patient population . METHODS We r and omly assigned 272 patients to receive nivolumab , at a dose of 3 mg per kilogram of body weight every 2 weeks , or docetaxel , at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS The median overall survival was 9.2 months ( 95 % confidence interval [ CI ] , 7.3 to 13.3 ) with nivolumab versus 6.0 months ( 95 % CI , 5.1 to 7.3 ) with docetaxel . The risk of death was 41 % lower with nivolumab than with docetaxel ( hazard ratio , 0.59 ; 95 % CI , 0.44 to 0.79 ; P<0.001 ) . At 1 year , the overall survival rate was 42 % ( 95 % CI , 34 to 50 ) with nivolumab versus 24 % ( 95 % CI , 17 to 31 ) with docetaxel . The response rate was 20 % with nivolumab versus 9 % with docetaxel ( P=0.008 ) . The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel ( hazard ratio for death or disease progression , 0.62 ; 95 % CI , 0.47 to 0.81 ; P<0.001 ) . The expression of the PD-1 lig and ( PD-L1 ) was neither prognostic nor predictive of benefit . Treatment-related adverse events of grade 3 or 4 were reported in 7 % of the patients in the nivolumab group as compared with 55 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced , previously treated squamous-cell NSCLC , overall survival , response rate , and progression-free survival were significantly better with nivolumab than with docetaxel , regardless of PD-L1 expression level . ( Funded by Bristol-Myers Squibb ; CheckMate 017 Clinical Trials.gov number , NCT01642004 . ) BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 
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Conclusions PD-1/PD-L1  blockades prolonged OS and PFS in epithelial carcinoma patients .
PD-L1 expression was a predictive factor for PFS but not predictive for OS .
Age , sex and ECOG score were excluded to predict any of the efficacy endpoints .
Smoking history and EGFR wild type were associated with extended OS in NSCLC patients