First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial.

IF 42.1 1区 医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2025-03-20 Epub Date: 2024-11-26 DOI:10.1200/JCO-24-01326
Christian Marth, Richard G Moore, Mariusz Bidziński, Sandro Pignata, Ali Ayhan, M Jesús Rubio, Mario Beiner, Marcia Hall, Christof Vulsteke, Elena Ioana Braicu, Kenzo Sonoda, Xiaohua Wu, Sophia Frentzas, André Mattar, Stephanie Lheureux, Xiaojun Chen, Kosei Hasegawa, Manuel Magallanes-Maciel, Chel Hun Choi, Mariia Shalkova, Diego Kaen, Peng-Hui Wang, Regina Berger, Chinyere E Okpara, Jodi McKenzie, Lili Yao, Robert Orlowski, Vivek Khemka, Lucy Gilbert, Vicky Makker
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引用次数: 0

Abstract

Purpose: Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len + pembro versus chemotherapy in first-line aEC.

Methods: Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis-tested hazard ratio [HR], 1.1).

Results: Eight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P = .246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients.

Conclusion: First-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.

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晚期子宫内膜癌一线来伐替尼加 Pembrolizumab 与化疗的对比:一项随机、开放标签的 III 期试验。
目的:在III期研究309/KEYNOTE-775中,对于既往接受过治疗的晚期或复发性子宫内膜癌(aEC),与化疗相比,来伐替尼+pembrolizumab(len+pembro)能显著改善无进展生存期(PFS)和总生存期(OS)。我们报告了III期、随机、开放标签欧洲妇科肿瘤网络试验-en9/LEAP-001研究(ClinicalTrials.gov标识符:NCT03884101)的结果,该研究评估了len+pembro与化疗在一线aEC中的疗效:III期至IV期或复发、放射学表现为EC、既往未接受过化疗或新辅助铂类化疗后疾病进展≥6个月的患者按1:1随机分配至来那替尼20毫克、每天一次加pembrolizumab 200毫克、每3周一次或紫杉醇175毫克/平方米加卡铂AUC 6毫克/毫升/分钟、每3周一次。主要终点是PFS和OS,在错配修复能力良好(pMMR)和所有患者人群中进行评估。在最终分析(FA)时,评估了len + pembro与化疗的OS非劣效性(多重调整,单侧名义α,.0159;空假设检验的危险比[HR],1.1):842名患者被随机分配(len + pembro,n = 420 [pMMR人群,n = 320];化疗,n = 422 [pMMR人群,n = 322])。在FA时(数据截止日期为2023年10月2日),pMMR人群中,len + pembro与化疗的中位PFS(95% CI)分别为9.6(8.2至11.9)个月和10.2(8.4至10.5)个月(危险比[HR],0.99[95%CI,0.82至1.21]),所有患者的中位OS为12.5(10.3至15.1)个月对10.2(8.4至10.4)个月(HR,0.91[95%CI,0.76至1.09];描述性分析)。pMMR人群的中位OS(95% CI)为30.9(25.4至37.7)个月(HR,1.02 [95% CI,0.83至1.26];非劣效P = .246,无统计学意义),在所有来访者中为37.7(32.2至43.6)个月对32.1(27.2至35.7)个月(HR,0.93 [95% CI,0.77至1.12])。331/420例(79%)与274/411例(67%)接受治疗的患者发生了≥3级治疗相关不良事件:一线len+pembro与化疗相比,在pMMR aEC患者的PFS或OS方面未达到预设的统计标准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Clinical Oncology
Journal of Clinical Oncology 医学-肿瘤学
CiteScore
41.20
自引率
2.20%
发文量
8215
审稿时长
2 months
期刊介绍: The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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