PMID- 27852042 OWN - NLM STAT- MEDLINE DCOM- 20180220 LR - 20220408 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 5 DP - 2017 Jan 31 TI - Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. PG - 8910-8920 LID - 10.18632/oncotarget.13315 [doi] AB - PURPOSE: Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents. METHODS: PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics. RESULTS: Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively. CONCLUSION: Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo. FAU - Costa, Ricardo AU - Costa R AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Carneiro, Benedito A AU - Carneiro BA AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Agulnik, Mark AU - Agulnik M AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Rademaker, Alfred W AU - Rademaker AW AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. AD - Northwestern University Department of Preventive Medicine, Chicago, Illinois, USA. FAU - Pai, Sachin G AU - Pai SG AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Villaflor, Victoria M AU - Villaflor VM AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Cristofanilli, Massimo AU - Cristofanilli M AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Sosman, Jeffrey A AU - Sosman JA AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. FAU - Giles, Francis J AU - Giles FJ AD - Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AD - Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA. LA - eng GR - P30 CA060553/CA/NCI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal/*adverse effects MH - Antibodies, Monoclonal, Humanized/*adverse effects MH - Antineoplastic Agents, Immunological/*adverse effects MH - Drug Approval MH - Humans MH - Neoplasms/*drug therapy/immunology/pathology MH - Nivolumab MH - Odds Ratio MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors/immunology MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome PMC - PMC5352453 OTO - NOTNLM OT - adverse events OT - anti-PD1 antibodies OT - hypothyroidism OT - meta-analysis OT - pruritus COIS- CONFLICTS OF INTEREST Ricardo Costa M.D., M.Sc.: In the past 2 years the author had research project funded, in whole or in part, by Bristol Myers Squibb. EDAT- 2016/11/17 06:00 MHDA- 2018/02/21 06:00 PMCR- 2017/01/31 CRDT- 2016/11/17 06:00 PHST- 2016/09/20 00:00 [received] PHST- 2016/10/13 00:00 [accepted] PHST- 2016/11/17 06:00 [pubmed] PHST- 2018/02/21 06:00 [medline] PHST- 2016/11/17 06:00 [entrez] PHST- 2017/01/31 00:00 [pmc-release] AID - 13315 [pii] AID - 10.18632/oncotarget.13315 [doi] PST - ppublish SO - Oncotarget. 2017 Jan 31;8(5):8910-8920. doi: 10.18632/oncotarget.13315.