TY - JOUR T1 - Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0779-6 VL - 7 IS - 1 SP - 341 AU - Puyuan Xing AU - Fan Zhang AU - Guoqiang Wang AU - Yu Xu AU - Chengcheng Li AU - Shouzheng Wang AU - Yiying Guo AU - Shangli Cai AU - Yan Wang AU - Junling Li Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/341.abstract N2 - Background Deciphering the correlation between immune-related adverse events (irAEs) categorized by organ system class and clinical benefit of immunotherapy is critical for clinical practice. The aim of this study is to investigate the incidence rates of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI).Methods PubMed, Embase and Cochrane library were searched for eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were included. Logit transformation of the irAE incidences was applied for the generation of pooled estimate and Pearson correlation coefficient was calculated to evaluate the correlation between irAE and ORR.Results 48 clinical trials involving 7936 patients treated with NIVO or NIVO+IPI were included. Compared to NIVO, NIVO+IPI led to more all-grade and grade 3 or higher irAEs categorized by system organ class (P < 0.05). The ORR of NIVO was positively correlated with the incidence rate of skin (r = 0.79, P < 0.001), gastrointestinal (r = 0.56, P = 0.006) and endocrine irAEs (r = 0.44, P = 0.05), but not hepatic, pulmonary and renal irAEs. The ORR of NIVO+IPI was positively correlated with the incidence rate of skin (r = 0.54, P = 0.04), and gastrointestinal irAEs (r = 0.60, P = 0.02), but not endocrine, hepatic, pulmonary and renal irAEs.Conclusion This meta-analysis summarizes the incidence rates of irAEs in patients with advanced solid tumours treated with NIVO or NIVO+IPI, and uncovers their correlations with ORR across multiple neoplasms. These findings highlight the potential of irAE to reflect response to NIVO or NIVO+IPI.Abbreviations:ALTAlanine aminotransferaseASTAspartate aminotransferaseCRCColorectal carcinomaCTLA-4Cytotoxic T lymphocyte associated antigen 4GGTGamma Glutamyl TranspeptidaseHCCHepatocellular carcinomaHNSCCHead and neck squamous cell carcinomairAEImmune-related adverse eventMeSHMedical subject headingsNIVONivolumabNIVO+IPINivolumab plus ipilimumabNSCLCNon-small cell lung cancerORRObjective response ratesOSOverall survivalPD-1Programmed cell death-1PD-L1Programmed cell death-ligand 1PFSProgressive-free survivalPRISMAPreferred Reporting Items for Systematic reviews and Meta-AnalysesRCCRenal cell carcinoma ER -