Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial.

Autor: Matsubara N; National Cancer Center Hospital East, Chiba, Japan., de Wit R; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Balar AV; Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA., Siefker-Radtke AO; The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zolnierek J; LUX MED Onkologia Hospital, Warsaw, Poland., Csoszi T; Jász-Nagykun-Szolnok County Hospital, Szolnok, Hungary., Shin SJ; Yosnei University College of Medicine, Seoul, South Korea., Park SH; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Atduev V; Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia., Gumus M; Istanbul Medeniyet University, Istanbul, Turkey., Su YL; Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan., Karaca SB; Tülay Aktaş Onkoloji Hastanesi, İzmir Bornova, Turkey., Cutuli HJ; Institute for Diagnosis and Metabolic Research (IDIM), Buenos Aires, Argentina., Sendur MAN; Ankara Yildirim Beyazıt University Faculty of Medicine and Ankara City Hospital, Ankara, Turkey., Shen L; Merck & Co., Inc., Rahway, NJ, USA., O'Hara K; Eisai LTD, Hatfield, UK., Okpara CE; Eisai LTD, Hatfield, UK., Franco S; Merck & Co., Inc., Rahway, NJ, USA., Moreno BH; Merck & Co., Inc., Rahway, NJ, USA., Grivas P; University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: pgrivas@uw.edu., Loriot Y; Gustave Roussy, Cancer Campus, Villejuif, France; Université Paris-Saclay, Villejuif, France. Electronic address: Yohann.loriot@gustaveroussy.fr.
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2024 Mar; Vol. 85 (3), pp. 229-238. Date of Electronic Publication: 2023 Sep 29.
DOI: 10.1016/j.eururo.2023.08.012
Abstrakt: Background: Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).
Objective: To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study.
Design, Setting, and Participants: Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled.
Intervention: Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily.
Outcome Measurements and Statistical Analysis: Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). An external data monitoring committee (DMC) regularly reviewed safety and efficacy data every 3 mo.
Results and Limitations: Between June 25, 2019 and July 21, 2021, 487 patients were allocated to receive lenvatinib plus pembrolizumab (n = 245) or placebo plus pembrolizumab (n = 242). The median time from randomization to the data cutoff date (July 26, 2021) was 12.8 mo (interquartile range, 6.9-19.3). The median PFS was 4.5 mo in the combination arm and 4.0 mo in the pembrolizumab arm (hazard ratio [HR] 0.90 [95% confidence interval {CI} 0.72-1.14]). The median OS was 11.8 mo for the combination arm and 12.9 mo for the pembrolizumab arm (HR 1.14 [95% CI 0.87-1.48]). Grade 3-5 adverse events attributed to trial treatment occurred in 123 of 241 patients (51%) treated with lenvatinib plus pembrolizumab and in 66 of 242 patients (27%) treated with placebo plus pembrolizumab. This trial was terminated earlier than initially planned based on recommendation from the DMC.
Conclusions: The benefit-to-risk ratio for first-line lenvatinib plus pembrolizumab was not considered favorable versus pembrolizumab plus placebo as first-line therapy in patients with advanced UC.
Patient Summary: Lenvatinib plus pembrolizumab was not more effective than pembrolizumab plus placebo in patients with advanced urothelial carcinoma.
(Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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