The integration of immunotherapy into chemotherapy regimens has revolutionized the initial treatment approach for advanced endometrial cancer. Monica H. Vetter, MD, emphasized the importance of patient selection and adherence to guideline-based decisions in this evolving landscape.
Immunotherapy's Impact on Standard of Care
Vetter stated, "A majority of us would now consider the addition of immunotherapy to chemotherapy, followed by immunotherapy maintenance, as standard of care for most of our patients with advanced endometrial cancer." She noted that while the benefit is more pronounced in patients with mismatch repair-deficient (dMMR) disease, data also support its use in those with mismatch repair-proficient (pMMR) disease.
Key Trials and FDA Approvals
The phase 3 RUBY (NCT03981796) and KEYNOTE-868 (NCT03914612) trials led to the FDA approvals of dostarlimab-gxly (Jemperli) plus chemotherapy and pembrolizumab (Keytruda) plus chemotherapy, respectively, for patients with primary advanced or recurrent endometrial cancer. These approvals have significantly altered the treatment paradigm.
Patient Selection Considerations
Vetter highlighted the importance of inclusion criteria, stating that differences in these criteria explain variations in the magnitude of benefit, particularly in pMMR groups. She also noted that NCCN Guidelines include dostarlimab usage for patients with uterine carcinosarcomas and that insurance companies may adhere strictly to the inclusion criteria from the KEYNOTE-868 and RUBY trials, affecting coverage for pembrolizumab versus dostarlimab.
Updated Survival Data
Updated overall survival (OS) data, especially in dMMR groups, are significant for both drugs. Vetter pointed to updated OS data from the RUBY trial presented at the 2024 Society of Gynecologic Oncology Annual Meeting. Although OS data for dostarlimab plus chemotherapy did not reach statistical significance in the pMMR group, there was still a 7-month difference between the dostarlimab regimen and the placebo regimen, which could be clinically significant for patients with pMMR disease who otherwise have a poor prognosis.
Treatment Regimen Selection
For patients with dMMR disease, Vetter prefers the dostarlimab regimen due to its wider indication. "Essentially, there are patients who are going to be candidates for dostarlimab who are not candidates for pembrolizumab, but not vice versa," she explained. For pMMR disease, she also leans towards dostarlimab, partly because the NCCN Guidelines include uterine carcinosarcomas and higher-risk patients with stage 3C1 disease without measurable disease.
Safety Profiles
The safety profiles of these chemoimmunotherapy regimens are reassuring, with no notable differences or safety signals compared to previous experiences with immunotherapies in endometrial cancer and other disease sites. Immunotherapies have an acceptable, anticipated toxicity profile that gynecologic oncologists are becoming increasingly comfortable managing.
Additional Considerations
When selecting a frontline chemoimmunotherapy regimen, Vetter advises using the regimen one is most comfortable with, given the similar adverse effects and toxicity profiles between the two regimens. She recommends sticking with the one you're most familiar with, especially with the constant advancements in treatment options.
