Impact of Peritoneal Metastasis on Overall Survival in Patients with Advanced Endometrial Cancer Receiving Lenvatinib plus Pembrolizumab

Purpose: The combination of lenvatinib plus pembrolizumab (LP) is a standard treatment for advanced or recurrent endometrial cancer. However, the optimal starting dose of lenvatinib is debated due to its toxicity profile. This study aimed to evaluate the effectiveness and safety of the LP regimen in a real-world setting and to investigate the impact of the lenvatinib starting dose on survival outcomes. Methods: We conducted a retrospective analysis of 33 patients with advanced or recurrent endometrial cancer treated with the LP regimen at Kansai Medical University Hospital 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 the Kaplan-Meier method and Cox proportional hazards models. 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 revealed distinct prognostic factors for PFS and OS. A lenvatinib starting dose of 20 mg was the sole independent predictor for improved PFS (aHR for <20 mg: 5.83; p=0.003). In contrast, the presence of peritoneal metastasis was the sole independent predictor for worse OS (aHR: 7.51; p=0.005). Conclusion: In this real-world analysis, LP therapy was effective and tolerable. We identified distinct prognostic factors for short-term and long-term survival: a 20 mg lenvatinib starting dose was critical for improving PFS. In contrast, peritoneal metastasis was identified as a strong independent predictor of poor OS even in the LP therapy cohort, suggesting a need for further therapeutic development for patients with peritoneal metastasis.