乐伐替尼联合帕博利珠单抗治疗晚期或复发性子宫内膜癌的预后因素：日本一项多中心队列研究的分析
Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan.
作者信息
Nagase Yoshikazu, Nakagawa Satoshi, Kobayashi Mariya, Kurahashi Hiroki, Ogimoto Hiromi, Tanaka Ayaka, Tsujie Tomoko, Shiomi Mayu, Otake Akiko, Masuhara Kanji, Yoshikawa Kenichi, Yotsumoto Fusanori, Kurita Tomoko, Yoshino Kiyoshi, Yoshioka Emi, Egawa-Takata Tomomi, Kudaka Wataru, Sekine Masayuki, Unno Hikari, Takemura Masahiko, Aso Saki, Kai Kentaro, Kobayashi Eiji, Yokoi Takeshi, Akada Masashi, Kakubari Reisa, Hisa Tsuyoshi, Matsuzaki Shinya, Ueda Yutaka
机构信息
Department of Obstetrics and Gynecology, Kaizuka City Hospital, Osaka, Japan.
Department of Obstetrics and Gynecology, The University of Osaka Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
出版信息
Int J Clin Oncol. 2025 Sep 6. doi: 10.1007/s10147-025-02842-x.
BACKGROUND
Lenvatinib plus pembrolizumab (LP) therapy has emerged as an effective treatment for patients with advanced or recurrent endometrial cancer. However, limited data are available regarding its outcomes in real-world settings. This study aimed to identify prognostic factors associated with the efficacy of LP therapy.
METHODS
This multicenter observational study was conducted across 15 institutions in Japan and examined patients with endometrial cancer, including uterine carcinosarcoma, who experienced disease progression after receiving at least one platinum-based chemotherapy, including adjuvant treatment, and subsequently received LP therapy. The prognostic factors for progression-free survival were assessed using a multivariate Cox proportional hazards model.
RESULTS
A total of 105 patients met the inclusion criteria. Improved progression-free survival was independently associated with performance status of 0 (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.23-0.75), platinum-free interval (PFI) of ≥ 6 months (aHR 0.46, 95% CI 0.28-0.78), histology of grade 1-2 endometrioid carcinoma (aHR 0.52, 95% CI 0.30-0.91), and relative dose intensity during the initial 8 weeks (8w-RDI) of lenvatinib of ≥ 50% (aHR 0.53, 95% CI 0.31-0.91). Patients with PFI of ≥ 6 months also demonstrated improved overall survival (HR 0.44, 95% CI 0.25-0.76) and objective response rate (44.0% versus 20.0%, P = 0.011) compared with those with PFI of < 6 months. Additionally, 8w-RDI of lenvatinib ≥ 50% was associated with improved overall survival (HR 0.53, 95% CI 0.30-0.92) compared to those with < 50%.
CONCLUSIONS
This study identified several novel prognostic factors for LP therapy. Among them, PFI may inform treatment selection for recurrent endometrial cancer following chemotherapy.
CLINICAL TRIAL REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 000049997.
背景
乐伐替尼联合帕博利珠单抗（LP）疗法已成为晚期或复发性子宫内膜癌患者的有效治疗方法。然而，关于其在真实世界中的疗效数据有限。本研究旨在确定与LP疗法疗效相关的预后因素。
方法
这项多中心观察性研究在日本的15家机构进行，研究对象为子宫内膜癌患者，包括子宫肉瘤患者，这些患者在接受至少一种含铂化疗（包括辅助治疗）后出现疾病进展，随后接受LP疗法。使用多变量Cox比例风险模型评估无进展生存期的预后因素。
结果
共有105例患者符合纳入标准。无进展生存期的改善与以下因素独立相关：体能状态为0（调整后风险比[aHR]0.42，95%置信区间[CI]0.23 - 0.75）、无铂间期（PFI）≥6个月（aHR 0.46，95% CI 0.28 - 0.78）、1 - 2级子宫内膜样癌组织学类型（aHR 0.52，95% CI 0.30 - 0.91）以及乐伐替尼初始8周（8w - RDI）的相对剂量强度≥50%（aHR 0.53，95% CI 0.31 - 0.91）。与PFI < 6个月的患者相比，PFI≥6个月的患者总生存期也有所改善（风险比[HR]0.44，95% CI 0.25 - 0.76），客观缓解率更高（44.0%对20.0%，P = 0.011）。此外，与8w - RDI < 50%的患者相比，乐伐替尼8w - RDI≥50%与总生存期改善相关（HR 0.53，95% CI 0.30 - 0.92）。
结论
本研究确定了LP疗法的几个新的预后因素。其中，PFI可为化疗后复发性子宫内膜癌的治疗选择提供参考。
临床试验注册
大学医院医学信息网络临床试验注册中心（UMIN - CTR）000049997。
Zotero 插件