Phase 3 CLEAR study in patients with advanced renal cell carcinoma: outcomes in subgroups for the lenvatinib-plus-pembrolizumab and sunitinib arms

Frontiers in Oncology

Oncology

Thomas Powles¹  Cixin He²  Viktor Grünwald³  Jodi McKenzie⁴  Chinyere E. Okpara⁵  Rodolfo Perini⁶  Camillo Porta⁷  Sun Young Rha⁸  Toni K. Choueiri⁹  Pablo Maroto^1,10  Robert Motzer^1,11  Tomas Buchler^1,12  María José Méndez-Vidal^1,13  Eric Winquist^1,14  Masatoshi Eto^1,15  Sung-Hoo Hong^1,16  Toshio Takagi^1,17  Joseph E. Burgents^1,18  Jeffrey C. Goh^1,19  Thomas E. Hutson^2,20  Evgeny Kopyltsov^2,21 

[1] Barts Cancer Institute and the Royal Free Hospital, Queen Mary University of London, London, United Kingdom;Biostatistics, Eisai Inc., Nutley, NJ, United States;Clinic for Medical Oncology and Clinic for Urology, University Hospital Essen, Essen, Germany;Clinical Research, Eisai Inc., Nutley, NJ, United States;Clinical Research, Eisai Ltd., Hatfield, United Kingdom;Clinical Research, Merck & Co., Inc., Rahway, NJ, United States;Department of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’, Bari, Italy;Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States;Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States;Department of Oncology, Charles University and Thomayer University Hospital, Prague, Czechia;Department of Oncology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC) Hospital Universitario Reina Sofía, Córdoba, Spain;Department of Oncology, University of Western Ontario, London, ON, Canada;Department of Urology, Kyushu University, Fukuoka, Japan;Department of Urology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea;Department of Urology, Tokyo Women’s Medical University, Tokyo, Japan;Global Clinical Development, Merck & Co., Inc., Rahway, NJ, United States;ICON Research, South Brisbane & University of Queensland, St Lucia, QLD, Australia;Medical Oncology, Texas Oncology, Dallas, TX, United States;State Institution of Healthcare Regional Clinical Oncology Dispensary, Omsk, Russia;

关键词: renal cell carcinoma;    lenvatinib;    pembrolizumab;    sunitinib;    bone metastases;    liver metastases;    lung metastases;    sarcomatoid histology;   

DOI  :  10.3389/fonc.2023.1223282

 received in 2023-05-15, accepted in 2023-07-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.MethodsIn CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.ResultsIn all the assessed subgroups, median PFS was longer with lenvatinib-plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (HR 0.33, 95% CI 0.21–0.52) and patients with sarcomatoid features (HR 0.39, 95% CI 0.18–0.84). Median OS favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95% CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95% CI 0.32–2.58); though for many groups, median OS was not reached. ORR also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.ConclusionEfficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC—irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.Clinical trial registrationClinicalTrials.gov, identifier NCT02811861

【 授权许可】

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Copyright © 2023 Grünwald, Powles, Eto, Kopyltsov, Rha, Porta, Motzer, Hutson, Méndez-Vidal, Hong, Winquist, Goh, Maroto, Buchler, Takagi, Burgents, Perini, He, Okpara, McKenzie and Choueiri