Recent clinical data suggests that lenvatinib plus pembrolizumab efficacy extends to difficult-to-treat nonendometrioid endometrial cancers. A retrospective study at Jichi Medical University Hospital evaluated clinical outcomes for patients with recurrent disease. Specifically, researchers examined rare variants like carcinosarcoma and mesonephric-like adenocarcinoma. Although these subtypes often carry a poor prognosis, the combination therapy showed meaningful clinical activity.

Clinical Outcomes and Lenvatinib Plus Pembrolizumab Efficacy

The study involved 26 patients, including 11 with nonendometrioid carcinoma. Notably, the objective response rate for the nonendometrioid group reached 33.3%. Furthermore, the disease control rate was exceptionally high at 90.9%. In comparison, the endometrioid group had a response rate of 22.2% and a disease control rate of 100%.

Median progression-free survival was 6.2 months for nonendometrioid types. However, patients with endometrioid histology achieved a longer median survival of 11.5 months. In addition, the median overall survival for nonendometrioid cases was 12.0 months. Consequently, these findings highlight the potential of this regimen in managing aggressive histological variants.

Safety and Prognostic Factors

Hypertension was the most frequent adverse event, occurring in 92.3% of patients. Moreover, hypothyroidism affected 65.4% of the cohort. As a result, histology and platinum-free intervals were not identified as independent prognostic factors for survival. Therefore, the treatment benefit remains consistent across various clinical subgroups. Further accumulation of patient data is warranted to validate these results in uncommon histologic types.

How effective is LP therapy for nonendometrioid endometrial cancer?

Research indicates an objective response rate of 33.3% and a disease control rate of 90.9% for nonendometrioid subtypes, including carcinosarcoma and mesonephric-like adenocarcinoma.

What are the primary side effects associated with this combination?

The most common adverse events are hypertension, which affects over 90% of patients, and hypothyroidism, seen in approximately 65% of cases.

Disclaimer: This content is for informational and educational purposes only. It is not intended as medical advice or as a substitute for professional healthcare guidance. Refer to the latest local and national guidelines for clinical practice.

References

1. Takahashi Y et al. Efficacy of lenvatinib plus pembrolizumab for recurrent endometrial cancer: a focus on the nonendometrioid histology including carcinosarcoma. Jpn J Clin Oncol. 2026 Mar 01. doi: undefined. PMID: 41764636.


2. Makker V et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437-448. doi: 10.1056/NEJMoa2108330.


3. Makker V et al. Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775. J Clin Oncol. 2026. doi: 10.1200/JCO.2025.