{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:23:55Z","timestamp":1790796235119,"version":"4.1.0"},"reference-count":64,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2017.00730","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T04:33:48Z","timestamp":1508301228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":415,"title":["Immune-Related Adverse Events Associated with Anti-PD-1\/PD-L1 Treatment for Malignancies: A Meta-Analysis"],"prefix":"10.3389","volume":"8","author":[{"given":"Peng-Fei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Ying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jun","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Xiang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0140-6736(16)32455-2","article-title":"Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial","volume":"389","author":"Balar","year":"2016","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","article-title":"Pembrolizumab as second-line therapy for advanced urothelial carcinoma","volume":"376","author":"Bellmunt","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s12916-015-0455-8","article-title":"Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis","volume":"13","author":"Bertrand","year":"2015","journal-title":"BMC Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Eng. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1200\/JCO.2009.26.7609","article-title":"Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates","volume":"28","author":"Brahmer","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Eng. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","volume":"366","author":"Brahmer","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.immuni.2016.04.023","article-title":"Targeting T Cell co-receptors for cancer therapy","volume":"44","author":"Callahan","year":"2016","journal-title":"Immunity"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1093\/annonc\/mdw174","article-title":"Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer","volume":"27","author":"Chatterjee","year":"2016","journal-title":"Ann. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1093\/annonc\/mdv182","article-title":"A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors","volume":"26","author":"Chen","year":"2015","journal-title":"Ann. Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5461","DOI":"10.1158\/1078-0432.CCR-15-2839","article-title":"Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma","volume":"22","author":"Choueiri","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"8910","DOI":"10.18632\/oncotarget.13315","article-title":"Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials","volume":"8","author":"Costa","year":"2017","journal-title":"Oncotarget"},{"key":"B13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ctrv.2016.02.003","article-title":"Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy","volume":"45","author":"Eigentler","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1016\/S0140-6736(16)00587-0","article-title":"Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial","volume":"387","author":"Fehrenbacher","year":"2016","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1056\/NEJMoa1602252","article-title":"Nivolumab for recurrent squamous-cell carcinoma of the head and neck","volume":"375","author":"Ferris","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1200\/JCO.2014.58.3708","article-title":"Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer","volume":"33","author":"Gettinger","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1200\/JCO.2016.66.9929","article-title":"Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer","volume":"34","author":"Gettinger","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","article-title":"Predictive biomarkers for checkpoint inhibitor-based immunotherapy","volume":"17","author":"Gibney","year":"2016","journal-title":"Lancet Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4015","DOI":"10.1200\/JCO.2015.62.3397","article-title":"Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer","volume":"33","author":"Hamanishi","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"B23","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1001\/jamadermatol.2015.2707","article-title":"Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab","volume":"152","author":"Hua","year":"2016","journal-title":"JAMA Dermatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.cell.2017.01.010","article-title":"Genomic and transcriptomic features of response to Anti-PD-1 therapy in metastatic melanoma","volume":"168","author":"Hugo","year":"2017","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1093\/annonc\/mdx008","article-title":"Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial","volume":"28","author":"Hui","year":"2017","journal-title":"Ann. Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1016\/S1470-2045(16)30364-3","article-title":"Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial","volume":"17","author":"Kaufman","year":"2016","journal-title":"Lancet Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fphar.2017.00049","article-title":"Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy","volume":"8","author":"Kumar","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Eng. J. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1126\/science.271.5256.1734","article-title":"Enhancement of antitumor immunity by CTLA-4 blockade","volume":"271","author":"Leach","year":"1996","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1200\/JCO.2015.65.9789","article-title":"Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a Phase Ib study","volume":"34","author":"Lesokhin","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/cpt.394","article-title":"Immune-related adverse events from immune checkpoint inhibitors","volume":"100","author":"Marrone","year":"2016","journal-title":"Clin. Pharmacol. Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3119","DOI":"10.1200\/JCO.2016.67.9761","article-title":"Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer","volume":"34","author":"Massard","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1200\/JCO.2014.58.1041","article-title":"Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab","volume":"33","author":"McDermott","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1200\/JCO.2015.63.7421","article-title":"Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase ia study","volume":"34","author":"McDermott","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/nature10673","article-title":"Cancer immunotherapy comes of age","volume":"2","author":"Mellman","year":"2011","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: a comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"B37","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/S1470-2045(17)30104-3","article-title":"Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study","volume":"18","author":"Morris","year":"2017","journal-title":"Lancet Oncol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1056\/NEJMoa1510665","article-title":"Nivolumab versus everolimus in advanced renal-cell carcinoma","volume":"373","author":"Motzer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S1470-2045(16)00175-3","article-title":"Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial","volume":"17","author":"Muro","year":"2016","journal-title":"Lancet Oncol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1200\/JCO.2015.64.8931","article-title":"Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study","volume":"34","author":"Nanda","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1001\/jamaoncol.2016.2453","article-title":"Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis","volume":"2","author":"Nishino","year":"2016","journal-title":"JAMA Oncol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1056\/NEJMc1505197","article-title":"Anti-PD-1-Related Pneumonitis during Cancer Immunotherapy","volume":"373","author":"Nishino","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"B44","doi-asserted-by":"publisher","first-page":"4286","DOI":"10.1158\/1078-0432.CCR-14-2607","article-title":"Phase I study of pembrolizumab (MK-3475; Anti-PD-1 monoclonal antibody) in patients with advanced solid tumors","volume":"21","author":"Patnaik","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S1470-2045(17)30007-4","article-title":"Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study","volume":"18","author":"Plimack","year":"2017","journal-title":"Lancet Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1001\/jama.2016.4059","article-title":"Association of pembrolizumab with tumor response and survival among patients with advanced melanoma","volume":"315","author":"Ribas","year":"2016","journal-title":"JAMA"},{"key":"B48","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/S1470-2045(15)00083-2","article-title":"Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial","volume":"16","author":"Ribas","year":"2015","journal-title":"Lancet Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0140-6736(16)32517-X","article-title":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial","volume":"389","author":"Rittmeyer","year":"2017","journal-title":"Lancet"},{"key":"B50","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/S1470-2045(15)70054-9","article-title":"Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial","volume":"16","author":"Rizvi","year":"2015","journal-title":"Lancet Oncol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"","journal-title":"New Eng. J. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/S0140-6736(14)60958-2","article-title":"Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial","volume":"384","author":"Robert","year":"2014","journal-title":"Lancet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"","journal-title":"N. Eng. J. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1016\/S0140-6736(16)00561-4","article-title":"Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial","volume":"387","author":"Rosenberg","year":"2016","journal-title":"Lancet"},{"key":"B55","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/S1470-2045(16)30066-3","article-title":"Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial","volume":"17","author":"Seiwert","year":"2016","journal-title":"Lancet Oncol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/S1470-2045(17)30065-7","article-title":"Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial","volume":"18","author":"Sharma","year":"2017","journal-title":"Lancet Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s10637-016-0347-6","article-title":"Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors","volume":"34","author":"Shimizu","year":"2016","journal-title":"Invest. New Drugs"},{"key":"B58","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1002\/ijc.30501","article-title":"Safety and efficacy of nivolumab in the treatment of cancers: a meta-analysis of 27 prospective clinical trials","volume":"140","author":"Tie","year":"2017","journal-title":"Int. J. Cancer"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N. Eng. J. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1200\/JCO.2013.53.0105","article-title":"Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab","volume":"32","author":"Topalian","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nrc.2016.36","article-title":"Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy","volume":"16","author":"Topalian","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"B62","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S1470-2045(15)70076-8","article-title":"Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial","volume":"16","author":"Weber","year":"2015","journal-title":"Lancet. Oncol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1158\/2326-6066.CIR-15-0193","article-title":"Phase I\/II study of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab","volume":"4","author":"Weber","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/S1470-2045(16)30167-X","article-title":"Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial","volume":"17","author":"Younes","year":"2016","journal-title":"Lancet Oncol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2017.00730\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T04:33:48Z","timestamp":1508301228000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphar.2017.00730\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,18]]},"references-count":64,"alternative-id":["10.3389\/fphar.2017.00730"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2017.00730","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,18]]},"article-number":"730"}}