Abstract 922: Comparison of adverse effects of different combination therapies of immune checkpoint inhibitors and radiotherapy: A systematic review and meta-analysis
Authors: Zhou Haiyu , Guo Zefeng , Wang Ting , Cai Liyu , You Peimeng 
Published: March 2024

Abstract
Background: Numerous ongoing trials are investigating cancer treatment combinations based on the combination of radiotherapy and immune checkpoint inhibitors. Understanding the toxicity profile of treatment-related adverse events is crucial. The purpose of this study is to comprehensively investigate the incidence and overview of treatment-related adverse events in different combination therapies involving radiotherapy and immune checkpoint inhibitors.
Methods: We conducted a systematic review and meta-analysis of different combination therapies involving radiotherapy and immune checkpoint inhibitors. We searched English-language articles published between January 1, 2000, and May 31, 2023, in Pubmed, Embase, and the Cochrane database, investigating globally approved therapies based on PD-1, PD-L1 inhibitors, or CTA-4. Only prospective trials reporting overall incidence rates or lists of treatment-related adverse events data were included, and studies recruiting fewer than 10 patients were excluded. Retrospective studies were also excluded to minimize the risk of bias. The primary outcomes were the overall incidence and overview of treatment-related adverse events of all grades and grade 3 or higher. Heterogeneity among studies was assessed using the I2 statistic. The summary measure for primary outcomes was incidence rate (95% CI). This protocol is registered in PROSPERO (CRD42023390147).
Results: We identified 1300 records, of which 50 studies (1655 patients) met the inclusion criteria. The incidence of treatment-related adverse reactions in the concurrent group was 76.0% (95% CI 73.5-78.4), and the incidence of grade 3 or higher adverse events was 23.5% (21.1-25.9). In the sequential group, the incidence of treatment-related adverse reactions was 75.9% (70.8-80.6), and the incidence of grade 3 or higher adverse events was 22.5% (18.0-27.5). In the induction group, the incidence of treatment-related adverse reactions was 72.8% (65.0-79.8), and the incidence of grade 3 or higher adverse events was 37.1% (29.4-45.3). The most common specific adverse event in the concurrent group was Fatigue (27.8% [25.2-30.6]); in the sequential group, it was Fatigue (43.3% [33.3-53.7]); in the induction group, it was Fatigue (71.4% [56.7-83.4]). Grade 3 or higher adverse events in the concurrent group was Lymphocyte Count Decreased (7.2% [5.4-9.4]); in the sequential group, it was Pneumonitis (11.1% [5.7-19.0]); in the induction group, it was Fatigue (10.5% [5.6-17.7]).
Conclusion: Our study provides comprehensive data on treatment-related adverse events in different combination therapies involving radiotherapy and immune checkpoint inhibitors. Our results provide an essential reference of toxicity profiles of radiotherapy combined with immune checkpoint inhibitors for clinicians in routine practice of cancer care.
Citation Format: Haiyu Zhou, Zefeng Guo, Ting Wang, Liyu Cai, Peimeng You. Comparison of adverse effects of different combination therapies of immune checkpoint inhibitors and radiotherapy: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 922.