DataSheet_2_Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis.docx

BackgroundNeoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations.
MethodsThis review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model.
ResultsSixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle.
ConclusionThis study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

背景：新辅助联合免疫治疗正在改变癌症患者的治疗格局。探索该新兴疗法相关免疫相关不良事件（immune-related adverse events, irAEs）的发生率，可为未来临床研究提供有价值的参考。

方法：本系统评价严格遵循系统评价与Meta分析首选报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA）指南开展。检索PubMed、Embase、Cochrane Library、美国临床肿瘤学会（American Society of Clinical Oncology, ASCO）及欧洲肿瘤内科学会（European Society of Medical Oncology, ESMO）官方网站自建库至2023年11月24日的所有相关文献。随后从纳入研究中提取所需数据，采用R软件分析免疫相关不良事件的合并发生率。亚组分析采用随机效应模型，按癌症类型与联合治疗类型分别计算免疫相关不良事件的合并发生率。

结果：本Meta分析共纳入16项研究，涉及501例患者。考虑到研究设计的异质性，我们将随机对照试验（randomized controlled trials, RCTs）与单臂研究分开分析。在随机对照试验中，任意级别免疫相关不良事件发生率为95.0%（95%置信区间[CI] 87.3~99.3），≥3级免疫相关不良事件发生率为24.0%（95%置信区间[CI] 13.7~36.0）。在单臂研究中，任意级别免疫相关不良事件发生率为89.4%（95%置信区间[CI] 75.0~98.0），≥3级免疫相关不良事件发生率为20.3%（95%置信区间[CI] 8.7~35.2）。在随机对照试验与单臂研究中，最常见的任意级别免疫相关不良事件均为皮疹与乏力，而最常见的≥3级免疫相关不良事件为肝功能异常与结肠炎。因免疫相关不良事件，随机对照试验中有9.4%的患者、单臂研究中有6.9%的患者未完成规定的新辅助治疗周期。

结论：本研究全面总结了新辅助联合免疫治疗中免疫相关不良事件的发生率。免疫相关不良事件的发生情况因癌症类型与联合治疗类型而异。本Meta分析可为临床医师管理癌症患者提供重要指导。

系统评价注册：https://www.crd.york.ac.uk/prospero，标识符CRD42023387969。