Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Jan 16 [Epub ahead of print]
Robert J Motzer, Camillo Porta, Masatoshi Eto, Thomas Powles, Viktor Grünwald, Thomas E Hutson, Boris Alekseev, Sun Young Rha, Jaime Merchan, Jeffrey C Goh, Aly-Khan A Lalani, Ugo De Giorgi, Bohuslav Melichar, Sung-Hoo Hong, Howard Gurney, María José Méndez-Vidal, Evgeny Kopyltsov, Sergei Tjulandin, Teresa Alonso Gordoa, Vadim Kozlov, Anna Alyasova, Eric Winquist, Pablo Maroto, Miso Kim, Avivit Peer, Giuseppe Procopio, Toshio Takagi, Shirley Wong, Jens Bedke, Manuela Schmidinger, Karla Rodriguez-Lopez, Joseph Burgents, Cixin He, Chinyere E Okpara, Jodi McKenzie, Toni K Choueiri, CLEAR Trial Investigators
Memorial Sloan Kettering Cancer Center, New York, NY., University of Bari "A. Moro," Bari, Italy., Kyushu University, Fukuoka, Japan., The Royal Free NHS Trust, London, United Kingdom., University Hospital Essen, Essen, Germany., Texas Oncology, Dallas, TX., P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia., Yonsei Cancer Center, Yonsei University Health System, Seoul, South Korea., University of Miami Sylvester Comprehensive Cancer Center, Miami, FL., ICON Research, South Brisbane & Queensland University of Technology, Brisbane, Queensland, Australia., Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada., IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Palacky University, and University Hospital Olomouc, Olomouc, Czech Republic., Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea., Macquarie University, Sydney, NSW, Australia., Maimonides Institute for Biomedical research of Cordoba (IMIBIC) Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba, Spain., State Institution of Healthcare "Regional Clinical Oncology Dispensary," Omsk, Russia., N N Blokhin National Medical Research Center for Oncology, Ministry of Health of the Russian Federation, Moscow, Russia., Hospital Universitario Ramón y Cajal, Madrid, Spain., State budgetary Health Care Institution "Novosibirsk Regional Clinical Oncology Dispensary," Novosibirsk, Russia., Prevoljskiy Region Medical Centre, Novgorod, Russia., Western University, London, Ontario, Canada., Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Seoul National University Hospital, Seoul, South Korea., Rambam Health Care Campus, Haifa, Israel., Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy., Tokyo Women's Medical University, Tokyo, Japan., Western Health, Melbourne, Victoria, Australia., Department of Urology and Transplantation Surgery, Klinikum Stuttgart, Stuttgart, Germany., Department of Urology, Medical University of Vienna, Vienna, Austria., Merck & Co, Inc, Rahway, NJ., Merck & Co, Inc, Kenilworth, NJ., Eisai Inc, Nutley, NJ., Eisai Ltd, Hatfield, UK., Dana-Farber Cancer Institute, Boston, MA.