PD-1/L1 抑制剂作为转移性结直肠癌一线治疗的疗效和安全性：一项荟萃分析。
Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis.
机构信息
The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, China.
出版信息
Front Immunol. 2024 Jul 19;15:1425596. doi: 10.3389/fimmu.2024.1425596. eCollection 2024.
OBJECTIVE
To evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC).
METHOD
Articles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs).
RESULTS
Totally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77).
CONCLUSION
Our results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.
目的
评估 PD-1/L1 抑制剂作为转移性结直肠癌（mCRC）一线治疗的疗效和安全性。
方法
在四个数据库（Pubmed、Embase、Web of Science 和 Cochrane Library）中检索从数据库创建到 2023 年 11 月 11 日评估 PD-1/L1 抑制剂用于 mCRC 的一线治疗的文章。进行荟萃分析以评估无进展生存期（PFS）、总生存期（OS）、完全缓解（CR）、部分缓解（PR）、疾病稳定（SD）、疾病进展（PD）、客观缓解率（ORR）、疾病控制率（DCR）和≥3 级治疗相关不良事件（trAEs）的发生率。
结果
共纳入 9 项研究进行荟萃分析。根据错配修复（MMR）状态和方案进行了亚组分析。在接受 PD-1/L1 抑制剂作为一线治疗的诊断为错配修复缺陷（dMMR）mCRC 的患者中，ORR 为 0.54（95%CI，0.39 至 0.68），中位 PFS 为 53.2 个月，≥3 级 trAEs 发生率为 0.33（95%CI，0.12 至 0.60），中位 OS 未确定。对于接受 PD-1/L1 抑制剂、抗血管内皮生长因子单克隆抗体和化疗联合治疗作为一线治疗的 MMR 功能正常（pMMR）mCRC 患者，ORR 为 0.62（95%CI，0.56 至 0.68），中位 PFS 为 10.1 个月，中位 OS 为 26.7 个月，≥3 级 trAEs 发生率为 0.59（95%CI，0.39 至 0.77）。
结论
我们的结果表明，将 PD-1/L1 抑制剂作为 dMMR mCRC 的一线治疗具有非常好的疗效，同时保持了可接受的安全性。在 pMMR mCRC 患者中，联合使用 PD-1/L1 抑制剂、抗血管内皮生长因子单克隆抗体和化疗作为一线治疗可提高 ORR。然而，肿瘤的长期预后并没有显著改善。
系统评价注册
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196，标识符 CRD42024506196。
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