Dr. Roque on the Importance of Biomarker Testing in Advanced Endometrial Cancer

Dario R. Roque, MD, assistant professor of Obstetrics and Gynecology (Gynecologic Oncology), Northwestern University’s Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern Medicine, discusses how biomarker testing can lead to more accurate and effective treatment selection in advanced endometrial cancer.

The differentiation of molecular subtypes within endometrial cancer continues to improve the application of personalized therapies, Roque begins. This trend is reflected in the increased use of immune checkpoint inhibitors (ICI), he says.

In April 2021, the ICI dostarlimab-gxly (Jemperli) received accelerated approval from the FDA for adult patients with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer who experienced disease progression with previous platinum-based chemotherapy. The agent received full approval in this indication in February 2023.

Pembrolizumab (Keytruda) monotherapy subsequently gained FDA approval in March 2022 for patients with microsatellite instability–high (MSI-H) or dMMR advanced endometrial cancer who have progressed on prior systemic therapy in any setting.

These approvals signify the need to test patients for molecular markers to better identify which patients will benefit from ICI monotherapies, Roque states.

Patients may also experience benefit from ICI combination regimens, such as lenvatinib (Lenvima) plus pembrolizumab, Roque continues. The addition of the TKI to pembrolizumab was evaluated in the phase 3 KEYNOTE-775 trial (NCT03517449). Results demonstrated that this combination led to significantly improved progression-free survival and overall survival vs physician's choice of chemotherapy in patients with advanced endometrial cancer.

Moreover, recent data have indicated the utility of testing patients for P53 mutations, Roque adds. Findings from the phase 3 SIENDO trial (NCT03555422) showed that patients with P53 wild-type endometrial cancer experienced significant benefit with selinexor (Xpovio) vs placebo as maintenance therapy.

Overall, these data highlight the importance of identifying molecular subtypes within endometrial cancer and indicate that biomarker testing should be performed more consistently in clinical practice, Roque concludes.

Editor's Note: Dr Roque reports serving on the advisory board for Myriad; he serves on a speaker'sbureau for Myraid and GlaxoSmithKline; he is a surgical proctor at Intuitive; he received funding from Bristol Myers Squibb