Efficacy and safety of combination therapy with lenvatinib and pembrolizumab in elderly patients with advanced endometrial cancer

Background. Currently, women over 65 years of age comprise a quarter of endometrial cancer (EC) patients, but this population remains underrepresented in clinical trials. The combination therapy with lenvatinib plus pembrolizumab has demonstrated a significant improvement in progression-free survival and overall survival in patients with mismatch repair system proficiency (pMMR/MSS) after a single prior treatment line. However, data on the efficacy and safety of this regimen in real-world clinical practice, especially in elderly patients, are limited.

Aim. To describe the efficacy and safety of EC therapy with lenvatinib and pembrolizumab in elderly patients.

Materials and methods. In this retrospective single-center study conducted at a Moscow hospital (December 2020 – March 2024), we collected data on the efficacy and safety of lenvatinib and pembrolizumab therapy in 26 patients over 65 years of age. Patients with pathologically confirmed EC without evidence of microsatellite instability were included. The primary endpoint of the study was progression-free survival; additionally, we evaluated the clinical characteristics of the patients, analyzed the objective response rate and the incidence of adverse events.

Results. The median age was 69 (65–81) years, 23 % of patients were older than 75 years. The performance status of 92.3 % of patients was classified as ECOG 0–1, endometrial adenocarcinoma was the most frequently detected type (61.5 % of cases), serous carcinoma was reported in 10 (38.5 %) patients. The median number of prior treatment lines was 3 (2–6). The objective response rate reached 25 %, and the disease control rate was 75 %. The median progression-free survival was 5.67 (1.4–35.3) months. Adverse events of any grade were noted in 24 (92.3 %) patients. Lenvatinib dose reduction was performed in 76.9 % of cases. The most frequent adverse events were arterial hypertension (in 16 (61.5 %) patients), fatigue (in 5 (19.2 %) patients), and diarrhea (in 3 (11.5 %) patients).

Conclusion. In this real-world clinical practice study in Russia involving patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR/MSS) over 65 years of age who received lenvatinib plus pembrolizumab, the efficacy and safety of the treatment were comparable to those reported in earlier studies, suggesting the feasibility of combination therapy in this population with appropriate attention to performance status and management of adverse events. Additional studies are required to evaluate the efficacy and safety of the combination therapy of lenvatinib and pembrolizumab in patients with a more severe functional status.