DataSheet_1_The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis.pdf

ObjectiveCombination treatment regimens consisting of both immune checkpoint inhibitors (ICI) and chemotherapeutic agents have emerged as the standard of care for a range of cancers. This network meta-analysis (NMA) examined the toxicity profiles and safety rankings of these different ICI-based combination regimens.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all randomized controlled trials (RCTs) published as of March 1, 2022 comparing two or more treatment regimens in which at least one arm was comprised of an ICI + platinum-based chemotherapeutic regimen. Treatment-related adverse events (AEs) of any grade and AEs of grade 3 or higher were the primary endpoints for this analysis, while specific AE types were secondary endpoints. This NMA combined both direct and indirect comparisons when analyzing odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) for different ICI-based treatment regimens.ResultsIn total, 33 RCTs enrolling 19,012 cancer patients were included in this NMA. Of the analyzed regimens, avelumab + chemotherapy and camrelizumab + chemotherapy were associated with a significantly greater risk of AEs of any grade relative to ipilimumab + chemotherapy, durvalumab + chemotherapy, or pembrolizumab + chemotherapy. No significant differences in the risk of AEs of grade 3 or higher were observed when comparing different ICI regimens. Hepatotoxicity and pyrexia were the most common AEs associated with atezolizumab + chemotherapy treatment. Ipilimumab + chemotherapy was associated with a relatively higher risk of gastrointestinal and skin toxicity. Skin toxicity and hypothyroidism were the major AEs associated with nivolumab + chemotherapy. Fatigue and pneumonia were the most common AEs respectively associated with sugemalimab + chemotherapy and pembrolizumab + chemotherapy regimens.ConclusionsOf the evaluated regimens, camrelizumab + chemotherapy and avelumab + chemotherapy were associated with significantly higher rates of AEs of any grade, whereas durvalumab and sintilimab were relatively safe PD-L1 and PD-1 inhibitors, respectively, when administered in combination with platinum-based chemotherapy. However, none of the evaluated ICI + chemotherapy regimens exhibited any differences with respect to the incidence of grade 3 or higher AEs, offering guidance that may be of value in routine clinical practice.

以免疫检查点抑制剂（ICI）和化疗药物相结合的治疗方案已成为多种癌症治疗的标准。本网络荟萃分析（NMA）旨在探讨这些不同ICI为基础的联合治疗方案的不良反应特征及安全性排序。方法上，通过检索PubMed、EMBASE、Web of Science和Cochrane Library数据库，收集截至2022年3月1日所有发表的随机对照试验（RCTs），以比较两种或两种以上治疗方案，其中至少一种治疗方案包含ICI+以铂为基础的化疗方案。本分析以任何等级的治疗相关不良事件（AEs）以及3级或以上等级的AEs为主要终点，而特定AE类型则为次要终点。在分析不同ICI治疗方案的概率比（ORs）和累积排名曲线下面积（SUCRA）时，本NMA结合了直接和间接比较。结果方面，共有33项RCTs纳入本NMA，纳入19,012名癌症患者。在分析的治疗方案中，阿维鲁单抗+化疗和卡瑞利珠单抗+化疗与依匹单抗+化疗、度伐鲁单抗+化疗或帕博利珠单抗+化疗相比，任何等级的AEs风险显著增加。在比较不同ICI方案时，3级或以上AEs的风险并无显著差异。肝毒性发热是与阿替利珠单抗+化疗治疗最常见的不良事件。依匹单抗+化疗与相对较高的胃肠道和皮肤毒性风险相关。皮肤毒性和甲状腺功能减退是与尼伏单抗+化疗治疗的主要AEs。疲劳和肺炎分别是与苏克利单抗+化疗和帕博利珠单抗+化疗方案最常见的AEs。结论方面，在评估的治疗方案中，卡瑞利珠单抗+化疗和阿维鲁单抗+化疗与任何等级的AEs发生率显著较高，而度伐鲁单抗和信迪利单抗作为相对安全的PD-L1和PD-1抑制剂，分别与铂类化疗联合使用。然而，所有评估的ICI+化疗方案在3级或以上AEs发生率方面并无显著差异，为临床实践提供了有价值的指导。