Descriptive analysis of the use of pembrolizumab in combination with lenvatinib in the treatment of endometrial cancer in four university hospitals in Quebec, Canada.

OBJECTIVES: Pembrolizumab (PEMBRO) in combination with lenvatinib (LENVA) in mismatch repair proficient (pMMR) tumors is a new option in the treatment of endometrial cancer (EC). Our objectives were to assess the real-life use of this combination, including progression-free survival (PFS), overall survival (OS), rate of adverse events (AE), as well as incidence of LENVA dose reductions and interruptions. METHODS: This multicenter retrospective single-arm cohort study evaluated patients that received the treatment between January 1st, 2020 and September 30th, 2023. Adult patients with advanced, recurrent or metastatic EC who received PEMBRO/LENVA were included. PFS and OS were estimated using Kaplan-Meier methods, and exploratory log-rank tests were performed to compare patients who initiated LENVA at 20 mg versus a lower dose. Cox hazard regression analyses were performed to assess the impact of covariates. RESULTS: A total of 84 patients were included. Median PFS and OS were 7.1 months (95 % CI, 4.5-9.7) and 17.9 months (95 % CI, 7.3-28.6), respectively. No statistical difference was observed in survival outcomes between 20 mg (n = 48) and less than 20 mg (n = 36) starting dosage subgroups. Endometrioid subtype showed significantly improved outcomes vs non-endometrioid for both PFS (HR 0.373, p = 0.008) and OS (HR 0.387, p = 0.035). All patients experienced AE (grade 3: 36.9 %). LENVA dose reductions were required in 78.6 % of patients, LENVA interruptions in 67.9 %, and LENVA discontinuation in 19 %. CONCLUSIONS: The efficacy results are similar to those reported by the pivotal trial KEYNOTE-775. Our study suggests that proactive measures may promote LENVA tolerance without apparent deleterious effects on efficacy.