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Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study
RJ. Motzer, C. Porta, M. Eto, T. Powles, V. Grünwald, TE. Hutson, B. Alekseev, SY. Rha, J. Merchan, JC. Goh, AA. Lalani, U. De Giorgi, B. Melichar, SH. Hong, H. Gurney, MJ. Méndez-Vidal, E. Kopyltsov, S. Tjulandin, TA. Gordoa, V. Kozlov, A....
Language English Country United States
Document type Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article
Grant support
P30 CA008748
NCI NIH HHS - United States
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
38227898
DOI
10.1200/jco.23.01569
Knihovny.cz E-resources
- MeSH
- Survival Analysis MeSH
- Quinolines * MeSH
- Phenylurea Compounds * MeSH
- Antibodies, Monoclonal, Humanized * MeSH
- Carcinoma, Renal Cell * pathology MeSH
- Humans MeSH
- Kidney Neoplasms * pathology MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Sunitinib adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Randomized Controlled Trial MeSH
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
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
Memorial Sloan Kettering Cancer Center New York NY
Merck and Co Inc Kenilworth NJ
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 Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia
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
References provided by Crossref.org
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