PMID- 35173819 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220501 IS - 1758-8340 (Print) IS - 1758-8359 (Electronic) IS - 1758-8340 (Linking) VI - 14 DP - 2022 TI - Adverse events induced by nivolumab and ipilimumab combination regimens. PG - 17588359211058393 LID - 10.1177/17588359211058393 [doi] LID - 17588359211058393 AB - BACKGROUND: No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naive malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens. METHODS: Four major electronic databases were searched; both interventional and observational studies were included. All primary cancer types were permitted. Patients should not have been previously treated with any anti-cancer medications. The frequency of AEs was pooled using a random-model meta-analysis using the generic inverse variance method. Protocol registration: UMIN000044090. RESULTS: Forty articles representing 48 populations with 4,677 patients were included in the study. The pooled frequencies for key indicators were as follows: any AE, 81.3% (95% confidence interval (CI) 77.5-85.1); grade 3 or higher AE, 40.6% (95% CI: 35.7-45.5); serious AE, 32.7% (95% CI: 22.4-43.1); AE leading to discontinuation, 28.3% (95% CI: 23.7-32.8); and treatment-related death, 0.7% (95% CI: 0.4-1.1). AEs with the highest incidence were fatigue (27.9%, 95% CI: 22.6-33.3), followed by diarrhea (26.0%, 95% CI: 21.5-30.5), pruritus (24.6%, 95% CI: 20.3-28.8), rash (24.0% 95% CI: 19.3-28.7), and elevated aspartate aminotransferase (21.2%, 95% CI: 14.9-27.5). Subgroup analyses demonstrated that N3I1, compared to N1I3, less frequently induced any AE (N1I3 95.7%, N3I1 84.5%, p = 0.003), grade 3 or higher AE (N1I3 64.3%, N3I1 35.7%, p < 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, p = 0.004). CONCLUSIONS: Approximately 40% of patients had grade 3 or higher AE. The N3I1 regimen was substantiated to trigger fewer any AEs, high grade AEs, and serious AE than the N1I3 regimen. CI - (c) The Author(s), 2022. FAU - Somekawa, Kohei AU - Somekawa K AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Horita, Nobuyuki AU - Horita N AUID- ORCID: 0000-0002-8200-0340 AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. FAU - Kaneko, Ayami AU - Kaneko A AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Tagami, Yoichi AU - Tagami Y AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Fukuda, Nobuhiko AU - Fukuda N AUID- ORCID: 0000-0002-8498-2915 AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Matsumoto, Hiromi AU - Matsumoto H AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Namkoong, Ho AU - Namkoong H AD - Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan. FAU - Fujiwara, Yu AU - Fujiwara Y AD - Department of Medicine, Icahn School of Medicine at Mount Sinai and Mount Sinai Beth Israel, New York, NY, USA. FAU - Minegishi, Kaoru AU - Minegishi K AD - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Fukumoto, Takeshi AU - Fukumoto T AD - Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Watanabe, Keisuke AU - Watanabe K AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Hara, Yu AU - Hara Y AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kobayashi, Nobuaki AU - Kobayashi N AUID- ORCID: 0000-0002-7064-320X AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kaneko, Takeshi AU - Kaneko T AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. LA - eng PT - Journal Article DEP - 20220211 PL - England TA - Ther Adv Med Oncol JT - Therapeutic advances in medical oncology JID - 101510808 PMC - PMC8841925 OTO - NOTNLM OT - antineoplastic agents OT - clinical trial OT - drug-related side effects and adverse reactions OT - monoclonal antibodies OT - neoplasms COIS- Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: K.W. received lecture fee outside of this work from Ono Pharmaceutical. N.K. received lecture fee outside of this work from Ono Pharmaceutical and Bristol Myers Squibb. T.K. received lecture fee outside of this work from Bristol Myers Squibb. The other authors nothing to declare. EDAT- 2022/02/18 06:00 MHDA- 2022/02/18 06:01 PMCR- 2022/02/11 CRDT- 2022/02/17 05:35 PHST- 2021/07/23 00:00 [received] PHST- 2021/10/20 00:00 [accepted] PHST- 2022/02/17 05:35 [entrez] PHST- 2022/02/18 06:00 [pubmed] PHST- 2022/02/18 06:01 [medline] PHST- 2022/02/11 00:00 [pmc-release] AID - 10.1177_17588359211058393 [pii] AID - 10.1177/17588359211058393 [doi] PST - epublish SO - Ther Adv Med Oncol. 2022 Feb 11;14:17588359211058393. doi: 10.1177/17588359211058393. eCollection 2022.