Efficacy and safety of pembrolizumab–lenvatinib in metastatic endometrial cancer: results from the French multicenter early access program
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Pembrolizumab-lenvatinib (P/L) is a standard option for patients with advanced or metastatic endometrial cancer (a/m EC) progressing after platinum-based chemotherapy, based on the KEYNOTE-775 trial. However, concerns remain regarding its real-world applicability, particularly in older, frailer patients and in aggressive histological subtypes underrepresented or excluded from pivotal trials. This study aimed to evaluate the effectiveness and tolerability of P/L in routine practice through the French early access program (EAP). PATIENTS AND METHODS: We conducted a multicenter retrospective analysis of patients treated within the national EAP between March 2022 and December 2023. Eligible patients had histologically confirmed a/m EC progressing after platinum. Pembrolizumab was administered at 200 mg every 3 weeks, and lenvatinib was initiated at up to 20 mg daily. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods, and prognostic factors explored with Cox regression. RESULTS: A total of 351 patients from 25 centers were included [median age 73 years; 21.5% Eastern Cooperative Oncology Group (ECOG) ≥2]. Carcinosarcomas represented 8.9% of cases. Median PFS was 6.0 months [95% confidence interval (CI) 5.7-8.3], and median OS was 21 months (95% CI 18.6-22.9). Mismatch repair-deficient status was strongly associated with prolonged PFS (16 versus 6 months, P < 0.001). Objective response rate at 6 months was 41%, with a clinical benefit rate of 68%. Independent adverse prognostic factors for PFS included ECOG >1, multiple metastatic sites, microsatellite stable status, and carcinosarcoma subtype. Reduced starting lenvatinib dose (37.2% of patients) did not adversely impact PFS. Permanent discontinuation of lenvatinib because of toxicity was observed in 96 patients (27.6%). CONCLUSIONS: P/L demonstrates meaningful activity in a broad real-world population, including older patients with more aggressive disease features and those starting at reduced lenvatinib doses. These findings support the sustained benefit of this combination beyond clinical trial settings, provided that lenvatinib is carefully monitored and doses are personalized.
Source: ESMO Open
Authors: D. Bello Roufai, L. Mansi, M.H. Diallo, J.-D. Fumet, E. Kalbacher, M. Airoldi, F. Cherifi, B. Hanvic, M. Auvray-Kuentz, B. Billemont, C. Gervais, R. Batti, S. Quesada, S. Betrian-Lagarde, A.-C. Hardy-Bessard, H. Vegas, K. Prulhiere-Corviole, L. Muzellec, P. Bouchaert, P. Corbaux, M. Chaix, T. Collot, D. Garbay-Decoopman, M.-A. Benderra, M. Kfoury, P. Augereau
Institutions: Institut Curie, Inserm, Centre Georges François Leclerc, Université Bourgogne Europe, Centre Jean Perrin, Hôpitaux Universitaires de Strasbourg, Centre François Baclesse, Centre Léon Bérard, Centre Eugène Marquis, Institut Sainte Catherine, Hôpital Européen Georges-Pompidou, Centre Hospitalier de Valence, Institut Regional du Cancer de Montpellier, Institut universitaire du cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Tours, Centre Hospitalier de Cornouaille, Centre Hospitalier Universitaire de Poitiers, Centre Hospitalier Universitaire de Saint-Étienne, CHU Dijon Bourgogne, Centre Hospitalier William Morey, Assistance Publique – Hôpitaux de Paris, Hôpital Tenon, Institut Paoli-Calmettes, Institut de Cancérologie de l'Ouest
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,910
Funders: ARCAGY-GINECO, Eisai, Institut Curie
OpenAlex ID: W7214740428