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PD-1/PD-L1 抑制剂联合卡铂和紫杉醇与卡铂和紫杉醇治疗原发性晚期或复发性子宫内膜癌的比较:一项随机临床试验的系统评价和荟萃分析。

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials.

机构信息

Oncology Research Center, Federal University of Pará, University Hospital João de Barros de Barreto, Rua dos Mundurucus, nº4487, Belém, 66073-000, PA, Brazil.

Federal University of Santa Catarina, Florianópolis, 88040-900, Santa Catarina, Brazil.

出版信息

BMC Cancer. 2023 Nov 29;23(1):1166. doi: 10.1186/s12885-023-11654-z.

Abstract

BACKGROUND

Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear.

METHOD

We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I statistics. R, version 4.2.3, was used for statistical analyses.

RESULTS

A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23-0.44; p < 0.001) and overall survival (OS) at 30 months (RR 3.13; 95% CI 1.26-7.78; p = 0.01) were significant in favor of the PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel group in the mismatch repair-deficient subgroup. However, there were no significant differences in the mismatch repair-proficient subgroup for PFS (HR 0.74; 95% CI 0.50-1.08; p = 0.117) or OS at 30 months (RR 2.24; 95% CI 0.79-6.39; p = 0.13).

CONCLUSION

Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer, with a significant benefit in the mismatch repair-deficient and high microsatellite instability population.

摘要

背景

紫杉醇和卡铂是治疗晚期或复发性子宫内膜癌的标准化疗药物。然而,将程序性细胞死亡 1(PD-1)/程序性死亡配体 1(PD-L1)抑制剂添加到化疗中的益处仍不清楚。

方法

我们检索了 PubMed、Scopus、Cochrane 和 Web of Science 数据库,以查找比较 PD-1/PD-L1 抑制剂联合卡铂和紫杉醇与卡铂和紫杉醇治疗原发性晚期或复发性子宫内膜癌的随机对照试验。我们计算了二项终点的风险比(HRs)或风险比(RRs),置信区间(CI)为 95%。我们使用 DerSimonian 和 Laird 随机效应模型进行所有终点分析。使用 I 统计量评估异质性。使用 R,版本 4.2.3,进行统计分析。

结果

共有三项研究和 1431 名患者纳入研究。与卡铂联合紫杉醇化疗相比,无进展生存期(PFS)率(HR 0.32;95%CI 0.23-0.44;p<0.001)和 30 个月时的总生存期(OS)(RR 3.13;95%CI 1.26-7.78;p=0.01)在错配修复缺陷亚组中,PD-1/PD-L1 抑制剂联合卡铂和紫杉醇组具有显著优势。然而,在错配修复功能良好的亚组中,PFS(HR 0.74;95%CI 0.50-1.08;p=0.117)或 30 个月时的 OS(RR 2.24;95%CI 0.79-6.39;p=0.13)均无显著差异。

结论

免疫治疗联合卡铂-紫杉醇显著提高了晚期或复发性子宫内膜癌患者的 PFS 和 OS,在错配修复缺陷和高微卫星不稳定性人群中获益更为显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4103/10688003/db907d6fe2a3/12885_2023_11654_Figa_HTML.jpg

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