Advances and Toxicity to Immunotherapy for Endometrial Cancer

Author(s): Meaghan Delahunty, Osedebamen Aigbe, Batoul Sadek, Keval Yerigeri

Endometrial cancer (EC) is the fifth most common cancer among women in the United States. Current therapy for EC involves a combination of surgery, chemotherapy, and/or radiation; however, these therapies have shown little efficacy in the treatment of advanced/recurrent EC. Immune checkpoint inhibitor (ICI) therapy is an emerging treatment modality that has demonstrated potential for the treatment of advanced/ recurrent EC. Leading ICI therapies for EC include pembrolizumab and dostarlimab, which are monoclonal antibodies that modulate the programmed death receptor-1 (PD-1) pathway. This review examines current understanding of the efficacy and safety profiles for both pembrolizumab and dostarlimab ICI therapies in the treatment of advanced/recurrent EC. Evidence regarding pembrolizumab and dostarlimab monotherapy has shown both efficacy and equivocal safety in the treatment of advanced/ recurrent high microsatellite instability (MSI-H) and mismatch repair deficient (dMMR) endometrial cancer. However, there is less efficacy in the treatment of microsatellite stable (MSS) or mismatch repair proficient (pMMR) EC. Studies examining pembrolizumab or dostarlimab in combination with standard chemotherapy (paclitaxelcarboplatin) report a synergistic effect compared to chemotherapy alone for both dMMR/MSI-H and pMMR/MSS patient populations; however, ICI-chemotherapy combinations revealed a larger number of treatment-related adverse events. The KEYNOTE-146 and KEYNOTE-775 trials demonstrated the robust efficacy and manageable side effect profile of pembrolizumab in combination with lenvatinib for the treatment of both dMMR/MSI-H and pMMR/MSS advanced/recurrent EC. Current research demonstrates that ICI therapies improve patient outcomes in advanced/recurrent EC, particularly in dMMR/MSI-H populations. Additional emerging and promising therapies for EC include chimeric antigen receptor (CAR)-T cell therapy. More research regarding best-practice treatment for advanced/recurrent EC is needed.