Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Hiromi Matsumoto; Kohei Somekawa; Nobuyuki Horita; Suguru Ueda; Megumi Kaneko; Ayami Kaneko; Nobuhiko Fukuda; Ami Izawa; Chisato Kamimaki; Katsushi Tanaka; Kota Murohashi; Hiroaki Fuji; Yoichi Tagami; Ayako Aoki; Keisuke Watanabe; Yu Hara; Nobuaki Kobayashi; Takeshi Kaneko

doi:10.1177/17588359231198453

Adverse events induced by durvalumab and tremelimumab combination regimens: a systematic review and meta-analysis

Ther Adv Med Oncol. 2023 Sep 13:15:17588359231198453. doi: 10.1177/17588359231198453. eCollection 2023.

Authors

Hiromi Matsumoto¹, Kohei Somekawa¹, Nobuyuki Horita², Suguru Ueda¹, Megumi Kaneko¹, Ayami Kaneko¹, Nobuhiko Fukuda¹, Ami Izawa¹, Chisato Kamimaki¹, Katsushi Tanaka¹, Kota Murohashi¹, Hiroaki Fuji¹, Yoichi Tagami¹, Ayako Aoki¹, Keisuke Watanabe¹, Yu Hara¹, Nobuaki Kobayashi¹, Takeshi Kaneko¹

Affiliations

¹ Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
² Chemotherapy Center, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

Abstract

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.

Keywords: clinical trial; drug-related adverse events; immune checkpoint inhibitor; monoclonal antibodies; neoplasms.

Publication types

Review