National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney 2050, Australia.
Australia New Zealand Gynecological Oncology Group, Camperdown 2050, Australia.
JNCI Cancer Spectr. 2024 Nov 1;8(6). doi: 10.1093/jncics/pkae101.
Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma.
We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses.
A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months).
Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.
化疗免疫疗法是复发性或晚期错配修复缺陷型子宫内膜癌患者的标准治疗方法。然而，尚不确定错配修复缺陷型晚期或复发性子宫内膜癌患者从化疗中获益是否低于错配修复型子宫内膜癌患者。
我们对晚期或复发性子宫内膜癌的随机对照试验（RCT）进行了荟萃分析，以确定错配修复缺陷型与错配修复型子宫内膜癌患者化疗获益的差异。检索了化疗结局数据，包括客观缓解率、无进展生存期（PFS）和总生存期。我们使用逆方差法对这些数据进行了汇总，并按错配修复状态检查了亚组差异。我们还通过从试验出版物的 Kaplan-Meier 曲线创建个体患者数据进行敏感性分析，比较了 PFS 和总生存期结局的差异。
共有 5 项 RCT 纳入了 1137 名参与者（错配修复缺陷型，26%；错配修复型，74%）。所有参与者均接受了基于卡铂的化疗。在客观缓解率（66.5% vs 64.0%；亚组差异 P = .20）、PFS（风险比[HR] = 0.93，95%置信区间[CI] = 0.77 至 1.12；P = .44；中位 PFS = 7.6 个月 vs 9.5 个月）或总生存期（HR = 1.03，95%CI = 0.73 至 1.44；P = .88；中位总生存期=未达到 vs 28.6 个月）方面，错配修复缺陷型和错配修复型亚组之间无差异。
在 RCT 中，一线铂类双联化疗治疗的错配修复缺陷型与错配修复型子宫内膜癌患者的客观缓解率、PFS 和总生存期相似。这些发现强调了将化疗与免疫检查点抑制剂联合使用的重要性，直到比较免疫检查点单独治疗与联合治疗的试验结果可用。
