The 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.
In 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.
In 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.
Efficacy 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.
ClinicalTrials.gov, identifier NCT02811861.
Frontiers in oncology. 2023 Aug 16*** epublish ***
Viktor Grünwald, Thomas Powles, Masatoshi Eto, Evgeny Kopyltsov, Sun Young Rha, Camillo Porta, Robert Motzer, Thomas E Hutson, María José Méndez-Vidal, Sung-Hoo Hong, Eric Winquist, Jeffrey C Goh, Pablo Maroto, Tomas Buchler, Toshio Takagi, Joseph E Burgents, Rodolfo Perini, Cixin He, Chinyere E Okpara, Jodi McKenzie, Toni K Choueiri
Clinic for Medical Oncology and Clinic for Urology, University Hospital Essen, Essen, Germany., Barts Cancer Institute and the Royal Free Hospital, Queen Mary University of London, London, United Kingdom., Department of Urology, Kyushu University, Fukuoka, Japan., State Institution of Healthcare Regional Clinical Oncology Dispensary, Omsk, Russia., Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea., Department of Biomedical Sciences and Human Oncology, University of Bari 'A. Moro', Bari, Italy., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States., Medical Oncology, Texas Oncology, Dallas, TX, United States., Department of Oncology, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC) Hospital Universitario Reina Sofía, Córdoba, Spain., Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea., Department of Oncology, University of Western Ontario, London, ON, Canada., ICON Research, South Brisbane & University of Queensland, St Lucia, QLD, Australia., Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Department of Oncology, Charles University and Thomayer University Hospital, Prague, Czechia., Department of Urology, Tokyo Women's Medical University, Tokyo, Japan., Global Clinical Development, Merck & Co., Inc., Rahway, NJ, United States., Clinical Research, Merck & Co., Inc., Rahway, NJ, United States., Biostatistics, Eisai Inc., Nutley, NJ, United States., Clinical Research, Eisai Ltd., Hatfield, United Kingdom., Clinical Research, Eisai Inc., Nutley, NJ, United States., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.