Efficacy of lenvatinib plus pembrolizumab for recurrent endometrial cancer: a focus on the nonendometrioid histology including carcinosarcoma.

[OBJECTIVE] To evaluate the efficacy and safety of lenvatinib plus pembrolizumab (LP) for recurrent endometrial cancer, focusing on nonendometrioid histologic types such as carcinosarcoma and other rare variants.

[METHODS] Patients with recurrent endometrial cancer treated with LP at Jichi Medical University Hospital between December 2021 and August 2025 were retrospectively reviewed. Out of 26 patients, 15 had endometrioid carcinoma, whereas 11 had nonendometrioid carcinoma, specifically carcinosarcoma (n = 6), mesonephric-like adenocarcinoma (n = 2), dedifferentiated carcinoma (n = 1), mixed carcinoma (clear cell and endometrioid histology, n = 1), and clear cell carcinoma (n = 1). Clinical outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Prognostic factors for PFS were explored using Cox regression.

[RESULTS] The ORR and disease control rates, respectively, were 33.3% and 90.9% in nonendometrioid carcinoma, compared to 22.2% and 100% in endometrioid carcinoma. The median PFS was 6.2 months for nonendometrioid and 11.5 months for endometrioid carcinoma (hazard ratio [HR] 1.75, P = .295), while the median OS was 12.0 and 38.2 months, respectively (HR 2.41, P = .202). On multivariate analysis, histology, platinum-free interval, and eight-week relative dose intensity were not identified as independent prognostic factors. The most frequent AEs were hypertension (92.3%) and hypothyroidism (65.4%).

[CONCLUSIONS] LP therapy demonstrated clinical activity in nonendometrioid carcinoma, including rare subtypes such as carcinosarcoma and mesonephric-like adenocarcinoma. Further accumulation of patients is warranted to validate its efficacy in these uncommon histologic types.