Next Steps After New Frontline Therapy for dMMR Endometrial Cancer

Matthew Powell, MD, professor of Obstetrics and Gynecology and chief of the Division of Gynecologic Oncology at Siteman Cancer Center, Washington University School of Medicine, discusses next steps and unmet needs following the phase 3 RUBY/ENGOT-EN6 study (NCT03981796) and the FDA approval of dostarlimab (Jemperli) in combination with chemotherapy for the treatment of patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer.

Following the positive progression-free survival results in the dMMR population vs chemotherapy alone, immune checkpoint inhibition plus chemotherapy is now a frontline therapy in endometrial cancer. Powell says the next steps are to research the molecular subtypes to see which patients benefit most and which patients don’t need this therapy in the frontline. Additionally, he says that it’s needed to investigate second-line therapy including antibody-drug conjugates following dostarlimab/chemotherapy.

According to Powell, there are many unmet needs as the rate of endometrial cancer is rising rapidly, which may be related to the obesity epidemic. Identifying patients before they develop incurable malignancies would be beneficial. Additionally, he says Black Americans have about twice as poor survival outcomes with endometrial cancer and tend to have aggressive disease, making it important to understand differences and disparities in underrepresented groups.

TRANSCRIPTION:

0:08 | The next steps [are] to further understand the molecular subtypes, and which patients benefit most, which patients maybe don't need this therapy, and understand then what we would do after if maybe this regimen doesn't work. So, for second line therapy, how do we add in some of the new therapies like antibody-drug conjugates, and other options we have beyond chemotherapy?

0:36 | Unfortunately, there's a lot of unmet needs in endometrial cancer. One, it's a disease where the rate is actually rising and rising fast. A lot of that has to do with our obesity epidemic. Targeting patients before they develop cancer would be ideal and there are some preventative strategies we're working on. But also focusing on the large disparity among our underrepresented groups, mostly Black patients [who] have about twice [as] worse survival. When they develop endometrial cancer, they tend develop a very aggressive type, and new interventions are definitely needed, and understanding why these differences exist are also crucial.