PMID- 37720498 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230921 IS - 1758-8340 (Print) IS - 1758-8359 (Electronic) IS - 1758-8340 (Linking) VI - 15 DP - 2023 TI - Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis. PG - 17588359231198453 LID - 10.1177/17588359231198453 [doi] LID - 17588359231198453 AB - BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). OBJECTIVE: We aimed to assess the frequency of AEs associated with DT. DESIGN: This study type is a systematic review and meta-analysis. DATA SOURCES AND METHODS: Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). RESULTS: Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups. CONCLUSIONS: The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy. CI - (c) The Author(s), 2023. FAU - Matsumoto, Hiromi AU - Matsumoto H AUID- ORCID: 0000-0002-4819-1454 AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 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 - Chemotherapy Center, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. FAU - Ueda, Suguru AU - Ueda S AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kaneko, Megumi AU - Kaneko M AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kaneko, Ayami AU - Kaneko A 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 - Izawa, Ami AU - Izawa A AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kamimaki, Chisato AU - Kamimaki C AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Tanaka, Katsushi AU - Tanaka K AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Murohashi, Kota AU - Murohashi K AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Fuji, Hiroaki AU - Fuji H 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 - Aoki, Ayako AU - Aoki A AD - Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, 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 PT - Review DEP - 20230913 PL - England TA - Ther Adv Med Oncol JT - Therapeutic advances in medical oncology JID - 101510808 PMC - PMC10501063 OTO - NOTNLM OT - clinical trial OT - drug-related adverse events OT - immune checkpoint inhibitor OT - monoclonal antibodies OT - neoplasms COIS- The authors declare that there is no conflict of interest. EDAT- 2023/09/18 06:42 MHDA- 2023/09/18 06:43 PMCR- 2023/09/13 CRDT- 2023/09/18 04:41 PHST- 2023/04/04 00:00 [received] PHST- 2023/08/15 00:00 [accepted] PHST- 2023/09/18 06:43 [medline] PHST- 2023/09/18 06:42 [pubmed] PHST- 2023/09/18 04:41 [entrez] PHST- 2023/09/13 00:00 [pmc-release] AID - 10.1177_17588359231198453 [pii] AID - 10.1177/17588359231198453 [doi] PST - epublish SO - Ther Adv Med Oncol. 2023 Sep 13;15:17588359231198453. doi: 10.1177/17588359231198453. eCollection 2023.