Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC).
To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study.
Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled.
Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily.
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.
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.
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.
Lenvatinib plus pembrolizumab was not more effective than pembrolizumab plus placebo in patients with advanced urothelial carcinoma.
European urology. 2023 Sep 29 [Epub ahead of print]
Nobuaki Matsubara, Ronald de Wit, Arjun Vasant Balar, Arlene O Siefker-Radtke, Jakub Zolnierek, Tibor Csoszi, Sang Joon Shin, Se Hoon Park, Vagif Atduev, Mahmut Gumus, Yu-Li Su, Saziye Burcak Karaca, Hernán Javier Cutuli, Mehmet A N Sendur, Liji Shen, Karen O'Hara, Chinyere E Okpara, Sonia Franco, Blanca Homet Moreno, Petros Grivas, Yohann Loriot
National Cancer Center Hospital East, Chiba, Japan., Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA., The University of Texas MD Anderson Cancer Center, Houston, TX, USA., LUX MED Onkologia Hospital, Warsaw, Poland., Jász-Nagykun-Szolnok County Hospital, Szolnok, Hungary., Yosnei University College of Medicine, Seoul, South Korea., Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia., Istanbul Medeniyet University, Istanbul, Turkey., Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan., Tülay Aktaş Onkoloji Hastanesi, İzmir Bornova, Turkey., Institute for Diagnosis and Metabolic Research (IDIM), Buenos Aires, Argentina., Ankara Yildirim Beyazıt University Faculty of Medicine and Ankara City Hospital, Ankara, Turkey., Merck & Co., Inc., Rahway, NJ, USA., Eisai LTD, Hatfield, UK., University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: ., Gustave Roussy, Cancer Campus, Villejuif, France; Université Paris-Saclay, Villejuif, France. Electronic address: .