Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, 12877Kitasato University, Minato-ku, Tokyo, Japan.
10873Development, Astellas Pharma Inc, Chuo-ku, Tokyo, Japan.
Cancer Control. 2022 Jan-Dec;29:10732748221140694. doi: 10.1177/10732748221140694.
The clinical efficacy of immune checkpoint inhibitors (CPIs) has been proven; however, it is also known that their efficacy as monotherapy is limited, with a response rate of 20% or less in solid tumors. The combination of CPIs and anticancer agents has been actively attempted in solid tumors area. In this systematic review and meta-analysis, we aimed to find favorable combination therapies of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors in terms of anti-tumor efficacy in clinical settings.
An electronic database search was performed using ClinicalTrials.gov, PubMed, and ASCO/ESMO annual meeting libraries. We included randomized or non-randomized trials designed to evaluate the efficacy and safety of combination therapies of PD-1/PD-L1 inhibitors and other anticancer drug-containing therapies. All clinical studies selected were solid tumors with objective response rate (ORR) data. The quality of the evidence was assessed with the Cochrane risk of bias tool or the Newcastle-Ottawa Scale. Meta-analysis used random effects models to pool results.
Sixteen studies involving 3793 patients were included in the primary analysis. These studies have a monotherapy group with PD-1/PD-L1 inhibitors as the control group or the in-study arm/cohort (1863 patients in the combination group with PD-1/PD-L1 inhibitors and 1930 patients in PD-1/PD-L1 inhibitor monotherapy). The pooled results showed that the combination of PD-1/PD-L1 inhibitors and other anticancer drugs significantly improved the ORR (relative risk [RR] = 1.79, 95% confidence interval [CI] 1.46, 2.20). In the subgroup analysis, PD-1/PD-L1 inhibitor plus DNA-synthesis or microtubule inhibitor led to a statistically significant improvement in the ORR compared to PD-1/PD-L1 inhibitor alone.
It was suggested that combinations of PD-1/PD-L1 inhibitors and potential immunogenic cell death (ICD) inducers improve the clinical anti-tumor efficacy, although updated meta-analyses based on the results of ongoing clinical trials are further needed.
免疫检查点抑制剂（CPIs）的临床疗效已得到证实；然而，也已知其作为单药治疗的疗效有限，在实体瘤中的反应率低于 20%。CPIs 与抗癌药物的联合已在实体瘤领域积极尝试。在这项系统评价和荟萃分析中，我们旨在寻找 PD-1（程序性死亡受体 1）或 PD-L1（程序性死亡受体配体 1）抑制剂的有利联合治疗方案，以在临床环境中获得抗肿瘤疗效。
使用 ClinicalTrials.gov、PubMed 和 ASCO/ESMO 年会文库进行电子数据库搜索。我们纳入了旨在评估 PD-1/PD-L1 抑制剂与其他含抗癌药物的联合治疗方案的疗效和安全性的随机或非随机试验。所有选择的临床研究均为实体瘤，具有客观缓解率（ORR）数据。使用 Cochrane 偏倚风险工具或纽卡斯尔-渥太华量表评估证据质量。使用随机效应模型对结果进行荟萃分析。
纳入了 16 项研究，共 3793 名患者。这些研究有一个单药组，使用 PD-1/PD-L1 抑制剂作为对照，或作为研究组/队列（联合组中有 1863 名患者使用 PD-1/PD-L1 抑制剂和其他抗癌药物，单药组中有 1930 名患者使用 PD-1/PD-L1 抑制剂）。汇总结果表明，PD-1/PD-L1 抑制剂与其他抗癌药物联合使用显著提高了 ORR（相对风险 [RR] = 1.79，95%置信区间 [CI] 1.46，2.20）。在亚组分析中，与 PD-1/PD-L1 抑制剂单药治疗相比，PD-1/PD-L1 抑制剂联合 DNA 合成或微管抑制剂可显著提高 ORR。
提示 PD-1/PD-L1 抑制剂与潜在的免疫原性细胞死亡（ICD）诱导剂的联合使用可提高临床抗肿瘤疗效，尽管需要基于正在进行的临床试验结果进行更新的荟萃分析。
