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.

Dana Farber Cancer Institute Boston MA

Department of Urology and Transplantation Surgery Klinikum Stuttgart Stuttgart Germany

Department of Urology Medical University of Vienna Vienna Austria

Eisai Inc Nutley NJ

Eisai Ltd Hatfield UK

Fondazione IRCCS Istituto Nazionale Tumori Milano Milan Italy

Hospital de la Santa Creu i Sant Pau Barcelona Spain

Hospital Universitario Ramón y Cajal Madrid Spain

ICON Research South Brisbane and Queensland University of Technology Brisbane Queensland Australia

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Juravinski Cancer Centre McMaster University Hamilton Ontario Canada

Kyushu University Fukuoka Japan

Macquarie University Sydney NSW Australia

Maimonides Institute for Biomedical research of Cordoba Hospital Universitario Reina Sofía Medical Oncology Department Córdoba Spain

Memorial Sloan Kettering Cancer Center New York NY

Merck and Co Inc Kenilworth NJ

Merck and Co Inc Rahway NJ

N N Blokhin National Medical Research Center for Oncology Ministry of Health of the Russian Federation Moscow Russia

P A Herzen Moscow Oncological Research Institute Moscow Russia

Palacky University and University Hospital Olomouc Olomouc Czech Republic

Prevoljskiy Region Medical Centre Novgorod Russia

Rambam Health Care Campus Haifa Israel

Seoul National University Hospital Seoul South Korea

Seoul St Mary's Hospital The Catholic University of Korea Seoul South Korea

State budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary Novosibirsk Russia

State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia

Texas Oncology Dallas TX

The Royal Free NHS Trust London United Kingdom

Tokyo Women's Medical University Tokyo Japan

University Hospital Essen Essen Germany

University of Bari A Moro Bari Italy

University of Miami Sylvester Comprehensive Cancer Center Miami FL

University of Pavia Pavia Italy

Western Health Melbourne Victoria Australia

Western University London Ontario Canada

Yonsei Cancer Center Yonsei University Health System Seoul South Korea

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ClinicalTrials.gov
NCT02811861