ArticleFrontiers in oncology2025
Toxicity and efficacy of lenvatinib plus pembrolizumab in advanced endometrial cancer: a real-world retrospective analysis.
Article in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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5 authors.
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Abstract
Background: 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.
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