Prognostic factors of lenvatinib plus pembrolizumab therapy for advanced or recurrent endometrial cancer: analysis of a multicenter cohort study in Japan

Background: Lenvatinib plus pembrolizumab (LP) therapy has emerged as an effective treatment for patients with advanced or recurrent endometrial cancer. However, limited data are available regarding its outcomes in real-world settings. This study aimed to identify prognostic factors associated with the efficacy of LP therapy. Methods: This multicenter observational study was conducted across 15 institutions in Japan and examined patients with endometrial cancer, including uterine carcinosarcoma, who experienced disease progression after receiving at least one platinum-based chemotherapy, including adjuvant treatment, and subsequently received LP therapy. The prognostic factors for progression-free survival were assessed using a multivariate Cox proportional hazards model. Results: A total of 105 patients met the inclusion criteria. Improved progression-free survival was independently associated with performance status of 0 (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.23–0.75), platinum-free interval (PFI) of ≥ 6 months (aHR 0.46, 95% CI 0.28–0.78), histology of grade 1–2 endometrioid carcinoma (aHR 0.52, 95% CI 0.30–0.91), and relative dose intensity during the initial 8 weeks (8w-RDI) of lenvatinib of ≥ 50% (aHR 0.53, 95% CI 0.31–0.91). Patients with PFI of ≥ 6 months also demonstrated improved overall survival (HR 0.44, 95% CI 0.25–0.76) and objective response rate (44.0% versus 20.0%, P = 0.011) compared with those with PFI of < 6 months. Additionally, 8w-RDI of lenvatinib ≥ 50% was associated with improved overall survival (HR 0.53, 95% CI 0.30–0.92) compared to those with < 50%. Conclusions: This study identified several novel prognostic factors for LP therapy. Among them, PFI may inform treatment selection for recurrent endometrial cancer following chemotherapy. Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 000049997.