Lenvatinib plus pembrolizumab in participants with advanced or recurrent endometrial cancer: Study 309/KEYNOTE-775 and ENGOT-en9/LEAP-001 post-(neo)adjuvant therapy outcomes
Year: 2026
Type: article
Abstract: OBJECTIVE: We report outcomes for the sub-group of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment in the phase 3 Study 309/KEYNOTE-775 (NCT03517449) and ENGOT-en9/LEAP-001 (NCT03884101). METHODS: Study 309/KEYNOTE-775 enrolled participants with advanced/recurrent/metastatic endometrial cancer with disease progression after 1 previous line of platinum-based chemotherapy (2 allowed if initially given as [neo]adjuvant therapy). ENGOT-en9/LEAP-001 enrolled participants with stage III-IV or recurrent, radiographically apparent endometrial cancer and no previous chemotherapy or disease progression ≥6 months after (neo)adjuvant platinum-based chemotherapy. In both trials, participants were randomized 1:1 to lenvatinib 20 mg once daily+pembrolizumab 200 mg every 3 weeks or chemotherapy (doxorubicin or paclitaxel in Study 309/KEYNOTE-775, carboplatin+paclitaxel in ENGOT-en9/LEAP-001). Overall survival and progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review) were primary endpoints. RESULTS: In Study 309/KEYNOTE-775 (n = 300), median (95% confidence interval) overall survival was 17.4 (14.0 to 22.8) months with lenvatinib+pembrolizumab and 13.3 (10.9 to 15.5) months with chemotherapy (hazard ratio [95% confidence interval], 0.67 [0.52 to 0.87]). Median (95% confidence interval) progression-free survival was 7.2 (5.6 to 8.0) and 3.9 (3.6 to 5.4) months (hazard ratio [95% confidence interval], 0.52 [0.40 to 0.68]). Objective response rates were 34.3% versus 16.6%. In ENGOT-en9/LEAP-001 (n = 121), median (95% confidence interval) overall survival was 35.4 (26.6 to not reached) months with lenvatinib+pembrolizumab and 22.1 (16.4 to 34.8) months with chemotherapy (hazard ratio [95% confidence interval], 0.66 [0.42 to 1.03]). Median (95% confidence interval) progression-free survival was 15.0 (8.3 to 21.0) and 8.3 (6.2 to 10.2) months (hazard ratio [95% confidence interval], 0.52 [0.33 to 0.81]). Objective response rates were 63.5% versus 43.1%. In both trials, the most common treatment-related adverse events with lenvatinib+pembrolizumab were hypertension (62.4%/60.3%) and hypothyroidism (58.2%/60.3%). CONCLUSIONS: In this sub-group analysis of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment, lenvatinib+pembrolizumab demonstrated better anti-tumor activity and favorable outcomes versus chemotherapy with manageable safety. Lenvatinib+pembrolizumab is approved for patients with advanced endometrial cancer and could be considered an effective treatment option in this sub-group.
Authors: Christian Marth, Domenica Lorusso, Mariusz Bidziński, Paolo Scollo, Mehmet Ali Vardar, Ana Oaknin, Diego Lucas Kaen, Angélica Nogueira-Rodrigues, David S. Miller, Kosei Hasegawa, Helen MacKay, Richard G. Moore, Alessandro D. Santin, Mayu Yunokawa, Ignacio Romero, Sandro Pignata, Sally Baron-Hay, Yong Man Kim, Amnon Amit, Sharad Ghamande, Anna Danska-Bidzinska, Rafal Tarnawski, Peng-Hui Wang, Zhou Yu, Brian M. Slomovitz, Chinyere E. Okpara, Jodi McKenzie, Robin Meng, Robert Orlowski, Vicky Makker
Institutions: Innsbruck Medical University, Universität Innsbruck, Humanitas University, Agostino Gemelli University Polyclinic, The Maria Sklodowska-Curie National Research Institute of Oncology, Università degli Studi di Enna Kore, Ospedale Cannizzaro, Cukurova University, Vall d'Hebron Institute of Oncology, National University of La Rioja, Universidade Federal de Minas Gerais, The University of Texas Southwestern Medical Center, Saitama International Medical Center, Saitama Medical University, Sunnybrook Health Science Centre, University of Toronto, Odette Cancer Centre, University of Rochester Medicine, University of Rochester, Yale University, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, Fundación Instituto Valenciano de Oncología, Spanish Ovarian Cancer Research Group, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Royal North Shore Hospital, CHA University Bundang Medical Center, CHA University, Technion – Israel Institute of Technology, Rambam Health Care Campus, Augusta University, National Yang Ming Chiao Tung University, Taipei Veterans General Hospital, Merck & Co., Inc., Rahway, NJ, USA (United States), Mount Sinai Medical Center, Eisai (United Kingdom), Eisai (United States), Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,800
OpenAlex ID: W7153807543