Gynecological tumors the use of pembrolizumab in advanced and recurrent endometrial cancer with mismatch repair deficiency (DMMR): a literature review

Introduction: Pembrolizumab is a key monoclonal antibody in immunotherapy, acting as a PD-1 receptor inhibitor. It is used to treat various malignant tumors, including advanced endometrial cancer, either alone or in combination with chemotherapy. Pembrolizumab shows promise in enhancing overall survival and progression-free survival, with a favorable safety profile.

Objective: This review examines the clinical effects of pembrolizumab on advanced/recurrent endometrial cancer with mismatch repair deficiency (dMMR), focusing on overall survival (OS), progression-free survival (PFS), response rates, and adverse events.

Method: This literature review was conducted using data from the PubMed databases. The search strategy involved the use of the MeSH descriptors “Pembrolizumab”, “Endometrial cancer advanced”, “mismatch repair”, combined with the Boolean operator “and.” The search was performed on August 12, 2024. In PubMed, 46 articles were identified. Articles with titles and abstracts relevant to the topic and published between 2023/24 were included. Studies not published in English or identified through citations were excluded. This process resulted in a final sample of 34 Results: The Phase III KEYNOTE-868 trial randomized 816 patients with advanced endometrial cancer into two groups: one receiving pembrolizumab and the other receiving placebo, both in conjunction with standard therapy of paclitaxel and carboplatin, followed by maintenance with pembrolizumab or placebo. Patients were further stratified into two cohorts based on mismatch repair status: deficient (dMMR) or proficient (pMMR), with median follow-ups of 12 and 7.9 months, respectively. At the 12-month mark in the dMMR cohort, the risk of disease progression or death was reduced by 70% with pembrolizumab compared to placebo; the disease progression-free survival rates were 74% and 38%, respectively (HR, 0.30; 95% CI, 0.19 to 0.48; P<0.001). In contrast, in the pMMR cohort with an average follow-up of 7.9 months, the median progression-free survival was 13.1 months with pembrolizumab compared to 8.7 months with placebo (HR, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Additionally, the addition of pembrolizumab did not appear to increase the frequency of adverse events.

Conclusion: Pembrolizumab, combined with chemotherapy and continued as maintenance therapy, significantly improves progression-free survival compared to placebo in both dMMR and pMMR endometrial cancer patients, showing promising results.

Corresponding author: Bianca Andrade Mello (e-mail: biaamello.bm@gmail.com).