Impact of Lenvatinib Starting Dose on PFS and Peritoneal Metastasis on OS in Advanced Endometrial Cancer

Purpose Lenvatinib plus pembrolizumab (LP) is standard treatment for advanced or recurrent endometrial cancer. However, the optimal starting dose of lenvatinib is debated due to its toxicity profile. This study evaluated the real-world effectiveness and safety of the LP regimen and investigated the impact of the lenvatinib starting dose on survival outcomes. Methods We retrospectively analyzed 33 patients with advanced or recurrent endometrial cancer treated with the LP regimen at our institution between February 2022 and August 2025. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Prognostic factors for survival were identified using Kaplan-Meier and Cox models. Variables for multivariate analysis were selected based on clinical relevance or p < 0.10 in univariate analysis. Results The median follow-up was 27.6 months. The ORR was 48.5%, with a median PFS of 6.7 months and a median OS of 21.7 months. Multivariate analysis for PFS confirmed a 20 mg lenvatinib starting dose as the sole independent predictor for improved PFS (aHR for < 20 mg: 5.83; 95% CI 1.84–18.43; p = 0.003). Exploratory multivariate analysis for OS identified peritoneal metastasis as the sole independent predictor for worse OS (aHR: 7.51; 95% CI 1.87–30.25; p = 0.005). Conclusion In this real-world analysis, LP therapy was effective and tolerable. We identified distinct prognostic factors: a 20 mg lenvatinib starting dose was critical for improving PFS, while peritoneal metastasis powerfully predicted poor OS. These findings highlight the importance of both initial dosing strategies and patient-specific tumor characteristics in managing this disease.