***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 We assessed the efficacy and safety of programmed cell death 1 ( PD-1 ) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study . We also sought to define and vali date an expression level of the PD-1 lig and 1 ( PD-L1 ) that is associated with the likelihood of clinical benefit . METHODS We assigned 495 patients receiving pembrolizumab ( at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks ) to either a training group ( 182 patients ) or a validation group ( 313 patients ) . We assessed PD-L1 expression in tumor sample s using immunohistochemical analysis , with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 ( proportion score ) . Response was assessed every 9 weeks by central review . RESULTS Common side effects that were attributed to pembrolizumab were fatigue , pruritus , and decreased appetite , with no clear difference according to dose or schedule . Among all the patients , the objective response rate was 19.4 % , and the median duration of response was 12.5 months . The median duration of progression-free survival was 3.7 months , and the median duration of overall survival was 12.0 months . PD-L1 expression in at least 50 % of tumor cells was selected as the cutoff from the training group . Among patients with a proportion score of at least 50 % in the validation group , the response rate was 45.2 % . Among all the patients with a proportion score of at least 50 % , median progression-free survival was 6.3 months ; median overall survival was not reached . CONCLUSIONS Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer . PD-L1 expression in at least 50 % of tumor cells correlated with improved efficacy of pembrolizumab . ( Funded by Merck ; KEYNOTE-001 Clinical Trials.gov number , NCT01295827 . ) BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to  receive  docetaxel  .  Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1  inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment Purpose BIRCH was design ed to examine the efficacy of atezolizumab , a humanized anti-programmed death-lig and 1 ( PD-L1 ) monoclonal antibody , in advanced non-small-cell lung cancer ( NSCLC ) across lines of therapy . Patients were selected on the basis of PD-L1 expression on tumor cells ( TC ) or tumor-infiltrating immune cells ( IC ) . Patients and Methods Eligible patients had advanced-stage NSCLC , no CNS metastases , and zero to two or more lines of prior chemotherapy . Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5 % of TC or IC ( TC2/3 or IC2/3 [ TC or IC ≥ 5 % PD-L1-expressing cells , respectively ] ) were enrolled . Atezolizumab 1,200 mg was administered intravenously every 3 weeks . Efficacy-evaluable patients ( N = 659 ) comprised three cohorts : first line ( cohort 1 ; n = 139 ) ; second line ( cohort 2 ; n = 268 ) ; and third line or higher ( cohort 3 ; n = 252 ) . The primary end point was independent review facility-assessed objective response rate ( ORR ; Response Evaluation Criteria in Solid Tumors [ RECIST ] version 1.1 ) . Secondary end points included median duration of response , progression-free survival , and overall survival ( OS ) . Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls . With a minimum of 12 months of follow-up , the independent review facility-assessed ORR was 18 % to 22 % for the three cohorts , and 26 % to 31 % for the TC3 or IC3 subgroup ; most responses are ongoing . Responses occurred regardless of EGFR or KRAS mutation status . The median OS from an up date d survival analysis ( minimum of 20 month follow up ) for cohort 1 was 23.5 months ( 26.9 months for TC3 or IC3 patients ) ; the median OS in cohorts 2 and 3 was 15.5 and 13.2 months , respectively . The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials . Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC , with good tolerability . PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab 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 ( 
    Output:
    
Conclusion Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile