PD-1和PD-L1抑制剂在晚期结直肠癌中的疗效与安全性：一项随机对照试验的荟萃分析
Efficacy and safety of PD-1 and PD-L1 inhibitors in advanced colorectal cancer: a meta-analysis of randomized controlled trials.
作者信息
Wang Zhenzi, Liu Yuan, Wang Kedi, Ma Liyan
机构信息
Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
出版信息
BMC Gastroenterol. 2024 Dec 18;24(1):461. doi: 10.1186/s12876-024-03554-8.
BACKGROUND
PD-1 and PD-L1 inhibitors have emerged as promising therapies for advanced colorectal cancer (CRC), but their efficacy and safety profiles require further evaluation. This meta-analysis aims to assess the efficacy and safety of PD-1/PD-L1 inhibitors in this patient population.
METHODS
A systematic review and meta-analysis were conducted following PRISMA guidelines, with data sourced from PubMed, Embase, CENTRAL, Web of Science, and CNKI up to August 3, 2024. Nine randomized controlled trials (RCTs) involving 1680 patients were included. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR), while safety was assessed through adverse events (AEs) and grade ≥ 3 AEs. Effect sizes were calculated using mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs).
RESULTS
Overall, the meta-analysis showed that PD-1/PD-L1 inhibitors did not significantly extend OS (MD = 0.86, 95% CI: -0.55, 2.27), but they significantly improved PFS (MD = 2.53, 95% CI: 0.92, 4.15). Additionally, PD-1/PD-L1 inhibitors did not significantly increase the ORR compared to controls (RR = 1.19, 95% CI: 0.99, 1.44). In terms of safety, PD-1/PD-L1 inhibitors did not significantly increase the incidence of overall AEs. Subgroup analysis further indicated that PD-1 inhibitors significantly improved OS (MD = 1.24, 95% CI: 0.20, 2.29) and PFS (MD = 6.27, 95% CI: 0.56, 11.97), while PD-L1 inhibitors did not have a significant impact on these outcomes. Additionally, PD-L1 inhibitors were associated with a higher risk of grade ≥ 3 AEs (RR = 1.29, 95% CI: 1.07, 1.57), a risk not observed with PD-1 inhibitors.
CONCLUSION
PD-1 inhibitors significantly improve PFS and OS in advanced CRC, making them a preferable option over PD-L1 inhibitors, which show limited efficacy and a higher risk of severe AEs. These findings support prioritizing PD-1 inhibitors in clinical practice for this patient group, while caution is warranted with PD-L1 inhibitors due to their safety concerns.
TRIAL REGISTRATION
PROSPERO (CRD42024611696).
背景
程序性死亡受体1（PD-1）和程序性死亡配体1（PD-L1）抑制剂已成为晚期结直肠癌（CRC）颇具前景的治疗方法，但其疗效和安全性仍需进一步评估。本荟萃分析旨在评估PD-1/PD-L1抑制剂在该患者群体中的疗效和安全性。
方法
按照系统评价和荟萃分析的首选报告项目（PRISMA）指南进行研究，数据来源于截至2024年8月3日的PubMed、Embase、Cochrane系统评价数据库、Web of Science和中国知网。纳入了9项涉及1680例患者的随机对照试验（RCT）。主要结局指标为总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR），通过不良事件（AE）和≥3级AE评估安全性。使用平均差（MD）和风险比（RR）及95%置信区间（CI）计算效应量。
结果
总体而言，荟萃分析显示，PD-1/PD-L1抑制剂未显著延长OS（MD = 0.86，95%CI：-0.55，2.27），但显著改善了PFS（MD = 2.53，95%CI：0.92，4.15）。此外，与对照组相比，PD-1/PD-L1抑制剂未显著提高ORR（RR = 1.19，95%CI：0.99，1.44）。在安全性方面，PD-1/PD-L1抑制剂未显著增加总体AE的发生率。亚组分析进一步表明，PD-1抑制剂显著改善了OS（MD = 1.24，95%CI：0.20，2.29）和PFS（MD = 6.27，95%CI：0.56，11.97），而PD-L1抑制剂对这些结局无显著影响。此外，PD-L1抑制剂与≥3级AE的较高风险相关（RR = 1.29，95%CI：1.07，1.57），PD-1抑制剂未观察到这种风险。
结论
PD-1抑制剂可显著改善晚期CRC患者的PFS和OS，使其成为比PD-L1抑制剂更优的选择，后者疗效有限且严重AE风险更高。这些研究结果支持在该患者群体的临床实践中优先使用PD-1抑制剂，而由于安全性问题，使用PD-L1抑制剂时需谨慎。
试验注册
国际前瞻性系统评价注册库（PROSPERO）（CRD42024611696）。
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