{"title":"lenvatinib + pembrolizumab治疗晚期或复发子宫内膜癌的预后因素：日本一项多中心队列研究分析","authors":"Yoshikazu Nagase, Satoshi Nakagawa, Mariya Kobayashi, Hiroki Kurahashi, Hiromi Ogimoto, Ayaka Tanaka, Tomoko Tsujie, Mayu Shiomi, Akiko Otake, Kanji Masuhara, Kenichi Yoshikawa, Fusanori Yotsumoto, Tomoko Kurita, Kiyoshi Yoshino, Emi Yoshioka, Tomomi Egawa-Takata, Wataru Kudaka, Masayuki Sekine, Hikari Unno, Masahiko Takemura, Saki Aso, Kentaro Kai, Eiji Kobayashi, Takeshi Yokoi, Masashi Akada, Reisa Kakubari, Tsuyoshi Hisa, Shinya Matsuzaki, Yutaka Ueda","doi":"10.1007/s10147-025-02842-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>This study identified several novel prognostic factors for LP therapy. Among them, PFI may inform treatment selection for recurrent endometrial cancer following chemotherapy.</p><p><strong>Clinical trial registration: </strong>University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 000049997.</p>","PeriodicalId":13869,"journal":{"name":"International Journal of Clinical Oncology","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan.\",\"authors\":\"Yoshikazu Nagase, Satoshi Nakagawa, Mariya Kobayashi, Hiroki Kurahashi, Hiromi Ogimoto, Ayaka Tanaka, Tomoko Tsujie, Mayu Shiomi, Akiko Otake, Kanji Masuhara, Kenichi Yoshikawa, Fusanori Yotsumoto, Tomoko Kurita, Kiyoshi Yoshino, Emi Yoshioka, Tomomi Egawa-Takata, Wataru Kudaka, Masayuki Sekine, Hikari Unno, Masahiko Takemura, Saki Aso, Kentaro Kai, Eiji Kobayashi, Takeshi Yokoi, Masashi Akada, Reisa Kakubari, Tsuyoshi Hisa, Shinya Matsuzaki, Yutaka Ueda\",\"doi\":\"10.1007/s10147-025-02842-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%.</p><p><strong>Conclusions: </strong>This study identified several novel prognostic factors for LP therapy. 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引用次数: 0
摘要
背景：Lenvatinib + pembrolizumab （LP）治疗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，有关其在现实环境中的结果的数据有限。本研究旨在确定与LP治疗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个机构进行，检查了包括子宫癌肉瘤在内的子宫内膜癌患者，这些患者在接受至少一次铂类化疗（包括辅助治疗）后出现疾病进展，随后接受LP治疗。使用多变量Cox比例风险模型评估无进展生存的预后因素。结果：105例患者符合纳入标准。改善的无进展生存期与以下因素独立相关：工作状态为0（校正风险比[aHR] 0.42, 95%可信区间[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（aHR 0.52, 95% CI 0.30-0.91）、lenvatinib最初8周的相对剂量强度(8w-RDI)≥50% （aHR 0.53, 95% CI 0.31-0.91）。与PFI患者相比，PFI患者≥6个月的总生存率（HR 0.44, 95% CI 0.25-0.76）和客观缓解率（44.0%对20.0%,P = 0.011）也有所改善。结论：本研究确定了LP治疗的几个新的预后因素。其中，PFI可为化疗后复发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（UMIN-CTR） 000049997。
Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan.
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.
期刊介绍：
The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.
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