Yunokawa Mayu, Abe Akiko, Wang Xiaofei, Toyohara Yusuke, Nimura Ryo, Komoto Takayuki, Misaka Satoki, Yoshimitsu Teruyuki, Ikki Ai, Kamata Mayumi, Nishino Shogo, Kanno Motoko, Fusegi Atsushi, Netsu Sachiho, Aoki Yoichi, Omi Makiko, Tanigawa Terumi, Okamoto Sanshiro, Nomura Hidetaka, Kanao Hiroyuki
Department of Gynecology, The Cancer Institute Hospital of Japanese Foundation of Cancer Research, 3-8-31 Ariake, KoutouKuu, Tokyo, 135-8550, Japan.
Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation of Cancer Research, Tokyo, Japan.
Int J Clin Oncol. 2025 Feb;30(2):371-379. doi: 10.1007/s10147-024-02667-0. Epub 2024 Dec 6.
Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary.
This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65 years, or with ECOG performance status 1-2.
Forty-five patients were analyzed: 21 (47%) were aged ˃ 65 years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5 months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6 months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65 years.
The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management.
对于晚期子宫内膜癌患者，采用乐伐替尼联合帕博利珠单抗方案进行二线治疗的有效管理是必要的。
这项回顾性研究纳入了接受乐伐替尼联合帕博利珠单抗方案治疗的子宫内膜癌患者。我们评估了无进展生存期（PFS）、总生存期（OS）以及不符合KEYNOTE775试验条件、年龄≥65岁或东部肿瘤协作组（ECOG）体能状态为1 - 2的患者的安全性。
共分析了45例患者：21例（47%）年龄>65岁，16例（36%）体能状态为1 - 2，15例（33%）不符合参加KEYNOTE775试验的条件。总体而言，中位PFS为8.5个月（95%置信区间[CI] 4.6 - 12.4），中位OS为15.6个月（95% CI 9.4 - NA）。不符合KEYNOTE775试验条件且体能状态为1 - 2的患者中位PFS显著缩短。体能状态为1 - 2的患者中位OS显著缩短。接受乐伐替尼联合帕博利珠单抗方案治疗的患者中，78%发生了3级以上不良事件（AE）。AE导致35例（78%）患者乐伐替尼剂量减少，分别有3例（7%）和5例（11%）患者停用乐伐替尼和帕博利珠单抗。所有患者首次乐伐替尼剂量减少的中位时间为1.5（0.92 - 2.3）个月，年龄>65岁的患者显著缩短。
在现实世界中，当前方案具有良好的疗效且安全性可控，乐伐替尼剂量可适当减少。然而，对于体能状态为1或2的患者、接受过大量治疗的患者以及存在器官功能障碍的患者，疗效可能较差。当前的治疗状况应反映相对于医疗环境和管理的真实世界数据。
