Dr Vetter on the Role of Trial Inclusion Criteria on Coverage for Pembrolizumab- and Dostarlimab-Based Regimens in Endometrial Cancer

"I think that the difference in the inclusion criteria is important because it explains some of the differences in terms of the magnitude of benefit that we saw, particularly in the pMMR group. It’s important to note those differences in inclusion criteria because from a practical standpoint, those are actually included in the NCCN Guidelines and have impacted some of the insurance approvals."

Monica H. Vetter, MD, gynecologic oncologist, Norton Cancer Institute, discusses how differences in patient inclusion criteria used in the phase 3 KEYNOTE-868 (NCT03914612) and RUBY (NCT04853576) trials have impact insurance approvals for pembrolizumab (Keytruda)- and dostarlimab-gxly (Jemperli)–based regimens in the treatment of patients with advanced or recurrent endometrial cancer.

In June 2024, the FDA approved pembrolizumab in combination with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma, based on data from KEYNOTE-868. In August 2024, the FDA approved dostarlimab in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, for the treatment of adult patients with primary advanced or recurrent endometrial cancer, based on data from RUBY.

Although both the pembrolizumab- and dostarlimab-based regimens are approved for the same patient population, the inclusion criteria in the respective trials have influenced their clinical applications and coverage decisions, Vetter explains. For example, the RUBY trial included patients with uterine carcinosarcomas, and this is reflected in the National Comprehensive Cancer Network (NCCN) Guidelines. Conversely, the KEYNOTE-868 trial excluded patients with uterine carcinosarcomas, which may explain why some insurers have denied pembrolizumab for patients who do not strictly meet the trial's inclusion parameters, Vetter explains.

The inclusion criteria for both study are included in the NCCN guidelines; as a result, payers often adhere to these guidelines when determining coverage. This has led to some instances where patients have been rejected for coverage of the pembrolizumab regimen who were then covered for the dostarlimab regimen.

Vetter concludes that addressing these nuances is essential for optimizing patient outcomes and their access to treatment.