RUBY试验4年生存结果：多塔利单抗联合化疗用于dMMR/MSI-H晚期或复发性子宫内膜癌
RUBY III期试验显示，在dMMR/MSI-H原发晚期或复发性子宫内膜癌患者中，多塔利单抗联合卡铂-紫杉醇（CP）对比安慰剂联合CP，中位随访55.6个月时持续改善无进展生存期（PFS）和总生存期（OS），死亡风险降低66%。4年时混合治愈模型估计多塔利单抗组治愈率为54%（95%CI 35%-72%），未观察新的安全性信号。
要点
- 多塔利单抗联合CP在dMMR/MSI-H晚期或复发性子宫内膜癌中持续改善PFS和OS。
- 中位PFS和OS未达到，死亡风险较安慰剂联合CP降低66%。
- 4年时混合治愈模型估计多塔利单抗组治愈潜力为54%（95%CI 35%-72%）。
核心结论
- 约4年随访时，多塔利单抗联合CP在dMMR/MSI-H原发晚期或复发性子宫内膜癌中显示持续缓解和长期生存获益，提示潜在治愈可能。
研究设计与样本
- 随机III期RUBY试验（NCT03981796）第1部分，患者1:1随机接受多塔利单抗+CP或安慰剂+CP，后续多塔利单抗或安慰剂至多3年或疾病进展。
- dMMR/MSI-H人群分析，中位随访55.6个月。
主要发现
- 多塔利单抗+CP对比安慰剂+CP显示持续OS和PFS获益，中位PFS和OS未达到，死亡风险降低66%。
- PFS曲线平台化，自第一次中期分析PFS分析后额外2.5年随访仅4例进展事件。
- 1年和2年时存活患者分别有>80%概率再存活3年和2年。
- 4年时混合治愈模型估计多塔利单抗组治愈率为54%（95%CI 35%-72%）。
- 未观察到新的安全性信号。
关键数值与推荐
- dMMR/MSI-H人群，中位随访55.6个月。
- 死亡风险降低66%（对比安慰剂+CP）。
- 4年时混合治愈模型估计治愈率54%（95%CI 35%-72%）。
临床怎么用
- 对于dMMR/MSI-H原发晚期或复发性子宫内膜癌，多塔利单抗联合卡铂-紫杉醇可作为一线治疗选择，具有长期生存获益和潜在治愈意图。
局限性
- 混合治愈模型为事后分析，治愈率为估计值，需谨慎解读。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVE: Dostarlimab+carboplatin-paclitaxel (CP) demonstrated significant improvement in progression-free survival (PFS) and clinically meaningful improvement in overall survival (OS) vs CP alone among patients with dMMR/MSI-H primary advanced/recurrent endometrial cancer (EC) in Part 1 of the randomized phase 3 RUBY trial (NCT03981796). We report updated efficacy and safety data with approximately 4 years of follow-up. METHODS: Patients were randomized 1:1 to receive dostarlimab+CP or placebo+CP followed by dostarlimab or placebo up to 3 years or until disease progression. Descriptive analyses of OS and PFS were conducted in the dMMR/MSI-H population (median follow-up, 55.6 months). Post hoc conditional survival analyses and a mixture cure model (MCM) fitted to PFS data to estimate the proportion of patients who had curative potential are presented to provide prognostic insights into long-term survival. RESULTS: Dostarlimab+CP demonstrated sustained OS and PFS benefits. Median PFS and OS were not reached with a 66% reduction in risk of death vs placebo+CP. PFS curve plateauing (only 4 progression events with additional 2.5 years follow-up since the previous PFS analysis at interim analysis 1) demonstrated durable disease control. Patients alive at the 1- and 2-year landmarks had >80% probability of remaining alive an additional 3 and 2 years, respectively. At 4 years, the MCM analysis estimated a cure rate with dostarlimab of 54% (95% CI 35%-72%). No new safety signals were observed. CONCLUSIONS: At 4 years, RUBY demonstrated sustained remission and long-term survival benefit, suggesting the potential for curative intent with dostarlimab+CP in patients with dMMR/MSI-H primary advanced or recurrent EC.
引用
- Powell MA, Roed H, Willmott LJ, et al. Four-year survival outcomes with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer in the RUBY trial. Gynecol Oncol. 2026. PMID: 42215378. doi:10.1016/j.ygyno.2026.05.008
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。