Analysis of Response to Pembrolizumab and Lenvatinib in pMMR Endometrial Cancers: A Retrospective Cohort Study.

Introduction: Among women with endometrial cancer, mismatch repair proficient (pMMR) patients often exhibit diminished responses to immunotherapy (IO). This study aims to evaluate real-world outcomes of immunotherapy-containing regimens for this patient population.

Methods: We analyzed charts of patients diagnosed with pMMR endometrial cancer who received an IO regimen between 01/01/2017-06/30/2024 for demographics, tumor characteristics, next-generation sequencing results, treatment dates and outcomes. Primary outcomes were PFS and OS of pembrolizumab/ lenvatinib (PL) and other IO-containing regimens in pMMR endometrial cancer.

Results: Twenty-six patients met inclusion criteria: 18 received treatment with PL, 8 received a different IO-containing regimen (IO group). Median age in the PL group was 68 (range: 51-80). The quantity of patients with grade 1, 2, and 3 disease was 3, 4, and 10, respectively. Median prior lines of therapy was 2 (range: 0-4); 8 had previously received IO. Median PFS in the PL group was 126 days (range: 20-1652) compared with 368 days (range: 42-714) in the IO group (p=0.043). Patients with lower-grade endometrial cancers in the PL group saw significantly improved OS when compared with higher-grade cancers (p=0.022). Additionally, 1 patient with high TMB had numerically improved OS, though statistical significance was not reached (p=0.33). Discontinuation due to toxicity was low: 2 attributed to lenvatinib, and none due to pembrolizumab.

Conclusions: In this real-world cohort of pMMR endometrial cancer patients treated with PL, the median PFS of 4.2 months was shorter than the 6.6 months reported in Study 309-KEYNOTE-775. Patients in the IO group had significantly longer PFS when compared with the PL group, though patients in the IO group had fewer prior lines of therapy. Small cohort sizes are a significant limitation of this analysis. Further study is needed to confirm whether the analyzed variables maintain potential significance in larger matched cohorts.