Nishio Shin, Nishikawa Tadaaki, Mori Masahiko, Kamiura Shoji, Sumi Toshiyuki, Yunokawa Mayu, Imai Yuichi, Kondo Eiji, Takehara Kazuhiro, Takano Hirokuni, Kudaka Wataru, Kado Nobuhiro, Yamagami Wataru, Kato Hidenori, Nishino Koji, Usami Tomoka, Hamanishi Junzo, Nii Masahiro, Takaya Itsumi, Okamoto Aikou
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan.
Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
J Gynecol Oncol. 2025 Jul;36(4):e118. doi: 10.3802/jgo.2025.36.e118.
OBJECTIVE: DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. METHODS: Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigator-assessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. RESULTS: In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32-1.12) and durvalumab + olaparib (0.44, 95% CI=0.22-0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. CONCLUSION: Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.
目的：DUO-E/GOG-3041/ENGOT-EN10（NCT04269200）研究表明，对于新诊断的晚期或复发性子宫内膜癌患者，在意向性治疗（ITT）人群中，度伐利尤单抗联合卡铂/紫杉醇，随后使用或不使用奥拉帕利的度伐利尤单抗方案，与单独使用卡铂/紫杉醇方案相比，在无进展生存期（PFS）方面有统计学意义且具有临床意义的改善。我们评估了DUO-E研究中日本亚组的疗效和安全性。 方法：新诊断为国际妇产科联盟（FIGO）III/IV期或复发性子宫内膜癌的患者按1:1:1随机分为对照组（卡铂/紫杉醇+度伐利尤单抗安慰剂[6个周期]，随后是度伐利尤单抗安慰剂+奥拉帕利安慰剂）、度伐利尤单抗组（卡铂/紫杉醇+度伐利尤单抗[每3周1,120 mg][6个周期]，随后是度伐利尤单抗[每4周1,500 mg]+奥拉帕利安慰剂）或度伐利尤单抗+奥拉帕利组（卡铂/紫杉醇+度伐利尤单抗[6个周期]，随后是度伐利尤单抗+奥拉帕利[每日两次，每次300 mg]）。双主要终点是研究者评估的度伐利尤单抗组和度伐利尤单抗+奥拉帕利组与对照组相比的PFS。这项预先指定的探索性分析评估了日本亚组的PFS和安全性。 结果：在日本亚组（n = 88）中，与对照组相比，PFS有利于度伐利尤单抗组（风险比=0.61，95%置信区间[CI]=0.32 - 1.12）和度伐利尤单抗+奥拉帕利组（0.44，95%CI = 0.22 - 0.85）；中位PFS分别为9.9个月和15.1个月，而对照组为9.5个月，18个月PFS率分别为37.0%和42.1%，对照组为22.2%。日本亚组的安全性概况总体上与完整安全性分析集以及各药物已确立的概况一致。 结论：日本亚组的疗效和安全性总体上与DUO-E研究ITT人群的结果一致。这项对DUO-E研究的日本亚组分析支持卡铂/紫杉醇+度伐利尤单抗，随后使用或不使用奥拉帕利的度伐利尤单抗作为晚期或复发性子宫内膜癌患者的新治疗选择，并且首次单独报告了这些方案在日本患者中的情况。
N Engl J Med. 2023-6-8
N Engl J Med. 2023-6-8
N Engl J Med. 2023-6-8
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