***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: PURPOSE Programmed death-1 ( PD-1 ) , an inhibitory receptor expressed on activated T cells , may suppress antitumor immunity . This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity , pharmacodynamics , and immunologic correlates . PATIENTS AND METHODS Thirty-nine patients with advanced metastatic melanoma , colorectal cancer ( CRC ) , castrate-resistant prostate cancer , non-small-cell lung cancer ( NSCLC ) , or renal cell carcinoma ( RCC ) received a single intravenous infusion of  anti-PD-1 ( MDX-1106 ) in dose-escalating six-patient cohorts at 0.3 , 1 , 3 , or 10 mg/kg , followed by a 15-patient expansion cohort at 10 mg/kg . Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy . RESULTS Anti-PD-1 was well tolerated : one serious adverse event , inflammatory colitis , was observed in a patient with melanoma who received five doses at 1 mg/kg . One durable complete response ( CRC ) and two partial responses ( PRs ; melanoma , RCC ) were seen . Two additional patients ( melanoma , NSCLC ) had significant lesional tumor regressions not meeting PR criteria . The serum half-life of anti-PD-1 was 12 to 20 days . However , pharmacodynamics indicated a sustained mean occupancy of > 70 % of PD-1 molecules on circulating T cells > or = 2 months following infusion , regardless of dose . In nine patients examined , tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment . CONCLUSION Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity . Exploration of alternative dosing regimens and combinatorial therapies with vaccines , targeted therapies , and /or other checkpoint inhibitors is warranted 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 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 . ) PURPOSE Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy . Several lines of evidence support the study of immunotherapy in triple-negative breast cancer ( TNBC ) . We assessed the safety and antitumor activity of the programmed cell death protein 1 ( PD-1 ) inhibitor pembrolizumab in patients with advanced TNBC . METHODS KEYNOTE-012 ( Clinical Trials.gov identifier : NCT01848834 ) was a multicenter , nonr and omized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive ( expression in stroma or ≥ 1 % of tumor cells by immunohistochemistry ) TNBC , gastric cancer , urothelial cancer , and head and neck cancer . This report focuses on the TNBC cohort . RESULTS Among 111 patients with TNBC whose tumor sample s were screened for PD-L1 expression , 58.6 % had PD-L1-positive tumors . Thirty-two women ( median age , 50.5 years ; range , 29 to 72 years ) were enrolled and assessed for safety and antitumor activity . The median number of doses administered was five ( range , 1 to 36 doses ) . Common toxicities were mild and similar to those observed in other tumor cohorts ( eg , arthralgia , fatigue , myalgia , and nausea ) , and included five ( 15.6 % ) patients with grade ≥ 3 toxicity and one treatment-related death . Among the 27 patients who were evaluable for antitumor activity , the overall response rate was 18.5 % , the median time to response was 17.9 weeks ( range , 7.3 to 32.4 weeks ) , and the median duration of response was not yet reached ( range , 15.0 to ≥ 47.3 weeks ) . CONCLUSION This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated , advanced TNBC . A single-agent phase II study examining a 200-mg dose given once every 3 weeks ( Clinical Trials.gov identifier : NCT02447003 ) is ongoing BACKGROUND Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer . As part of the phase 1b KEYNOTE-012 study , we aim ed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . METHODS This study was a multicentre , open-label , phase 1b trial done at 13 cancer research centres in the USA , Israel , Japan , South Korea , and Taiwan . We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-o 
    Output:
    
Conclusions and Relevance Our study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens .
Patients on combination therapy  are at increased risk of thyroid dysfunction and hypophysitis