Efficacy and safety of pembrolizumab with or without lenvatinib in recurrent uterine carcinosarcoma: a real-world single-center study.

[OBJECTIVE] Uterine carcinosarcoma (UCS) is a rare, aggressive endometrial cancer with limited treatment options for recurrence. The role of immunotherapy in UCS remains unclear. This study aimed to evaluate the efficacy and safety of pembrolizumab with or without lenvatinib in recurrent UCS.

[METHODS] We retrospectively analyzed 43 patients with recurrent UCS treated with pembrolizumab monotherapy (n = 9) or in combination with lenvatinib (n = 34) at a single center between 2018 and 2025. We analyzed clinicopathologic features, treatment response, survival outcomes and adverse events (AEs) graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

[RESULTS] Median progression-free survival (PFS) was 5 months and overall survival (OS) was 14 months. Objective response rate (ORR) was 37.5 % and disease control rate (DCR) was 67.5 %. The combination showed longer median PFS (5 vs. 3 months) and OS (19 vs. 7 months) compared with monotherapy, without statistical significance (PFS p = 0.99; OS p = 0.25). In exploratory multivariable analyses, larger tumor size was associated with shorter PFS (HR 2.73, 95 % CI 1.18-6.28) and OS (HR 5.36, 95 % CI 1.84-15.63). The most frequent AEs were hand-foot syndrome (29.4 %) and hypothyroidism (26.5 %), but no treatment-related deaths were observed.

[CONCLUSIONS] Pembrolizumab with or without lenvatinib demonstrated modest efficacy with a manageable safety profile in recurrent UCS, although monotherapy outcomes remain exploratory due to the small sample size. This real-world study supports the potential role of immunotherapy for select UCS patients and highlights the need for prospective trials.