High Effectiveness of Lenvatinib Plus Pembrolizumab in the NSMP/MMRd Molecular Subtype of Endometrial Cancer: A Real-World Data Analysis

Abstract

Abstract Background: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has identified four risk groups for the prognosis of endometrial cancer (EC). However, the prognostic impact of these subgroups on lenvatinib (LEN) plus pembrolizumab (PEM) administered as subsequent therapy after relapse is unknown. This study aimed to explore the effectiveness and safety of LEN/PEM therapy for recurrent EC using the ProMisE molecular classification. Methods:This single-center retrospective study included patients who underwent LEN/PEM therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subtypes using immunohistochemistry (IHC). The response rate, progression-free survival (PFS), and adverse events were evaluated using electronic medical records. The study was approved by the hospital’s ethics committee (approval number: MH2022-093). Results: This study enrolled 20 patients, who underwent a median follow-up of 10.7 months [95% confidence interval (CI): 8.9-12.4]. The best overall response rate was 60.0% (36.1–80.9) and the median PFS was 9.3 months (4.4-14.3). The median PFS in the p53abn group (n=8) was 3.2 months (2.3-4.2); however, PFS did not reach the median (p = 0.001) in the MMRd/NSMP group (n=12). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and a response was observed in all cases, irrespective of the molecular subtype. No treatment-related deaths occurred. Conclusion: The IHC-based ProMisE molecular classification system provides useful information for patient selection for LEN/PEM therapy.