Lenvatinib Dose Reductions Help Sustain Therapy in Endometrial Cancer

Susana M. Campos, MD, MPH, clinical director of the Division of Gynecologic Oncology and director of Educational Initiatives at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, shared practical strategies for managing the adverse effects of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) in endometrial cancer, including diarrhea and hypertension. Toxicity is a major driver of treatment discontinuation with this combination, and heavily pretreated patients often tolerate the regimen differently than the trial population did. Although the clinical trial starting dose of lenvatinib was 20 mg daily in the phase 3 KEYNOTE-775 study (NCT03517449), Campos described how she starts most pretreated patients at a lower dose in practice and adjusts based on tolerability, aiming to keep patients on a consistent, sustained exposure to the drug rather than cycling on and off therapy in response to toxicity.

Transcript:

CancerNetwork: Adverse effects for lenvatinib and pembrolizumab were highlighted, which included diarrhea and hypertension. What dose titration or management strategies do you recommend to help patients remain on therapy?

Campos: This has been debated often. Most patients start at a lower dose because they’ve been pretreated. The starting dose in the clinical trial was 20 mg. We’ve often found that very hard to tolerate in terms of hypertension, hand-foot syndrome, and the like. In my clinical practice, I start at 14 mg per day. If I can go up to 20 mg, I do; often I do not. I start at 14 mg. If patients are doing well, we stay at 14 mg. However, I’m very keen to dose reduce if [intolerable] toxicities ensue. I usually drop to 10 mg, and I’ve even kept patients on 8 mg of lenvatinib with pembrolizumab and gotten activity. You just have to learn how to titrate the drug so that patients can maintain a consistent exposure. I’m always very concerned if we start and stop, then what are patients seeing of this agent? In my clinical practice, I start at a lower dose and try to remain consistent.

Reference

Makker V, Colombo N, Casado A, et al. Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775. J Immunother Cancer. 2026;14(2):e013713. doi:10.1136/jitc-2025-013713