Immunotherapy in advanced endometrial cancer with microsatellite instability: A systematic review.

Abstract

Background: Endometrial cancer with microsatellite instability (MSI) involves 30% of diagnosed cases. There are some uncertainty about second-line treatment, after platinum-based first-line treatment. The aim of this study was to perform a systematic review on the scientific evidence of immunotherapies for endometrial cancer with MSI.

Methods: PubMed and Embase databases were searched up to May 28, 2024. We included clinical trials about patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) diagnosed with advanced and/or metastatic endometrial cancer who had previously received platinum-based chemotherapy. Clinical trials with a dMMR or MSI-H population size of less than 10 patients were discarded. Efficacy results in overall survival, progression-free survival and objective response rate were used to determine the most interesting drugs. A safety analysis of therapies was developed.

Results: Fifty-four studies were found in a systematic search. Fourteen clinical trials were selected. The following drugs were evaluated: pembrolizumab monotherapy, pembrolizumab plus lenvatinib, durvalumab, durvalumab-tremelimumab combination, dostarlimab, nivolumab and avelumab. The greatest numerical efficacy effect was achieved by pembrolizumab, followed by pembrolizumab in combination with lenvatinib. The most common adverse events were fatigue and gastrointestinal disorders.

Conclusion: The efficacy of pembrolizumab and pembrolizumab-lenvatinib regimen appears promising. However, studies with larger sample size, longer follow-up and comparative design with subgroup analysis based on differences in microsatellite repair mechanisms are needed for proper therapeutic positioning.