Impact of peritoneal metastasis on overall survival in patients with advanced endometrial cancer receiving lenvatinib plus pembrolizumab

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. 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. 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. In exploratory multivariable analysis adjusting for age ≥ 75 years and ECOG PS ≥ 1, a lenvatinib starting dose < 20 mg (vs. 20 mg) was associated with shorter PFS (aHR 5.83; 95% CI 1.84–18.43; p = 0.003). In contrast, peritoneal metastasis (present vs. absent) was independently associated with shorter OS (aHR 7.51; 95% CI 1.87–30.25; p = 0.005). In this real-world cohort, LP therapy was effective and tolerable. In exploratory analyses, lenvatinib starting dose and peritoneal metastasis showed distinct associations with PFS and OS, respectively; however, non-random dose selection and baseline imbalances limit causal interpretation. These findings should be considered hypothesis-generating and warrant prospective validation, particularly for patients with peritoneal metastasis.