ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1622253
This article is part of the Research TopicAdvances in Diagnosis and Treatment of Endometrial CancerView all 6 articles
Toxicity and Efficacy of Lenvatinib Plus Pembrolizumab in Advanced Endometrial Cancer: A Real-World Retrospective Analysis
Provisionally accepted
- 1Institute of Cancer, Northwell Health, Lake Success, New York, United States
- 2St. John’s University, Queens, NY, United States
- 3Northwell Health, New York, United States
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The treatment landscape for advanced recurrent endometrial cancer (EC) has been transformed with the introduction of lenvatinib and pembrolizumab, supported by results from the KEYNOTE-775 trial. However, the recommended 20 mg daily lenvatinib dose often results in significant toxicity, limiting its use in clinical practice. Objective: To evaluate the toxicity and efficacy of reduced (≤10 mg) versus higher (>10 mg) initial doses of lenvatinib combined with pembrolizumab in patients with advanced recurrent EC. Methods: In this retrospective cohort study, patients with EC treated with lenvatinib and pembrolizumab were stratified by initial lenvatinib dose into reduced (≤10 mg) and higher (>10 mg) groups. Study endpoints included progression-free survival (PFS), overall survival (OS) and treatment-related toxicity. Results: Of the 92 patients included, 62% initiated lenvatinib at ≤10 mg and only 14.1% received the recommended 20 mg dose. Baseline characteristics were comparable between groups, except for age (71.2 vs. 67.5 years; p = 0.003). Grade ≥2 adverse events occurred in 74% of patients, with half experiencing treatment interruptions, and 36% discontinuations, primarily due to fatigue, diarrhea, or thromboembolic events. While unadjusted PFS and OS did not differ significantly between groups (p = 0.074 and p = 0.148, respectively), age-adjusted analysis showed significantly higher hazard of progression or death in the reduced-dose group (HR: 2.92; 95% CI: 1.32-6.44; p = 0.008). Conclusion: This is the largest real-world study to date evaluating initial lenvatinib dosing strategies in advanced EC. Our findings suggest that although reduced starting doses (≤10 mg) are commonly used to mitigate toxicity, they may compromise efficacy. These results challenge current prescribing patterns and emphasize the need for prospective studies to define optimal dosing strategies.
Keywords: endometrial cancer, microsatellite-stable (MSS), microsatellite instability (MSI), KEYNOTE-775 trial, Lenvatinib, Pembrolizumab, Dose optimization, adverse events
Received: 02 May 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Barbi, Lee, Rahman, Cheng and John. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Veena Susan John, Institute of Cancer, Northwell Health, Lake Success, New York, United States
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