***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 
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    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 Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & Purpose To increase awareness , outline strategies , and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor ( ICPi ) therapy .  Methods A multidisciplinary , multi-organizational panel of experts in medical oncology , dermatology , gastroenterology , rheumatology , pulmonology , endocrinology , urology , neurology , hematology , emergency medicine , nursing , trialist , and advocacy was convened to develop the clinical practice guideline . Guideline development involved a systematic review of the literature and an informal consensus process . The systematic review focused on guidelines , systematic review s and meta-analyses , r and omized controlled trials , and case series published from 2000 through 2017 . Results The systematic review identified 204 eligible publications . Much of the evidence consisted of systematic review s of observational data , consensus guidelines , case series , and case reports . Due to the paucity of high- quality evidence on management of immune-related adverse events , recommendations are based on expert consensus . Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented . While management varies according to organ system affected , in general , ICPi therapy should be continued with close monitoring for grade 1 toxicities , with the exception of some neurologic , hematologic , and cardiac toxicities .  ICPi therapy may be suspended for most grade 2 toxicities , with consideration of resuming when symptoms revert to grade 1 or less . Corticosteroids may be administered . Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids ( prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d ) . Corticosteroids should be tapered over the course of at least 4 to 6 weeks . Some refractory cases may require infliximab or other immunosuppressive therapy . In general , permanent discontinuation of ICPis is recommended with grade 4 toxicities , with the exception of endocrinopathies that have been controlled by hormone replacement . Additional information is available at www.asco.org/supportive-care- guidelines and www.asco.org/ guidelines wiki BACKGROUND Pembrolizumab is a humanized monoclonal antibody against programmed death 1 ( PD-1 ) that has antitumor activity in advanced non-small-cell lung cancer ( NSCLC ) , with increased activity in tumors that express programmed death lig and 1 ( PD-L1 ) . METHODS In this open-label , phase 3 trial , we r and omly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50 % of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab ( at a fixed dose of 200 mg every 3 weeks ) or the investigator 's choice of platinum-based chemotherapy .  Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression . The primary end point , progression-free survival , was assessed by means of blinded , independent , central radiologic review . Secondary end points were overall survival , objective response rate , and safety . RESULTS Median progression-free survival was 10.3 months ( 95 % confidence interval [ CI ] , 6.7 to not reached ) in the pembrolizumab group versus 6.0 months ( 95 % CI , 4.2 to 6.2 ) in the chemotherapy group ( hazard ratio for disease progression or death , 0.50 ; 95 % CI , 0.37 to 0.68 ; P<0.001 ) . The estimated rate of overall survival at 6 months was 80.2 % in the pembrolizumab group versus 72.4 % in the chemotherapy group ( hazard ratio for death , 0.60 ; 95 % CI , 0.41 to 0.89 ; P=0.005 ) . The response rate was higher in the pembrolizumab group than in the chemotherapy group ( 44.8 % vs. 27.8 % ) , the median duration of response was longer ( not reached [ range , 1.9 + to 14.5 + months ] vs. 6.3 months [ range , 2.1 + to 12.6 + ] ) , and treatment-related adverse events of any grade were less frequent ( occurring in 73.4 % vs. 90.0 % of patients ) , as were grade 3 , 4 , or 5 treatment-related adverse events ( 26.6 % vs. 53.3 % ) . CONCLUSIONS In patients with advanced NSCLC and PD-L1 expression on at least 50 % of tumor cells , pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy . ( Funded by Merck ; KEYNOTE-024 Clinical Trials.gov number , NCT02142738 . ) Context : Immune checkpoint blockade is associated with endocrine-related adverse events . Thyroid dysfunction during pembrolizumab therapy , an anti-programmed cell death 1 ( PD-1 ) receptor monoclonal antibody , remains to be fully characterized . Objective : To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction . Design and Setting : Thyroid function was monitored prospect ively in melanoma patients who initiated pembrolizumab within an exp and ed access program at a referral oncology center . 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography ( 18FDG-PET/CT ) was review ed in cases compatible with inflammatory thyroiditis . Patients : Ninety-nine patients with advanced melanoma ( age , 26.3–93.6 years ; 63.6 % females ) who received at least one administration of pembrolizumab .  Main Outcome Measures : Patient characteristics , thyroid function ( TSH , free T4 ) , thyroid autoantibodies , and 18FDG-PET/CT . Results : Eighteen adverse events of thyroid dysfunction were observed in 17 patients . Thyrotoxicosis occurred in 12 patients , of which nine evolved to hypothyroidism . Isolated hypothyroidism was present in six patients . Levothyroxine therapy was required in 10 of 15 hypothyroid patients . Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases . Diffuse increased 18FDG uptake by the thyroid gl and was observed in all seven thyrotoxic patients who progressed to hypothyroidism . Conclusions : Thyroid dysfunction is common in melanoma patients treated with pembrolizumab . Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations . Serial measurements of thyroid function tests are 
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Therefore , there is a significant increase in developing thyroid dysfunction in advanced or metastatic NSCLC patients treated with Pembrolizumab