Pushing Forward With Molecularly-Driven Precision Medicine in Endometrial Cancer

In season 4, episode 8 of Targeted Talks, Ruchi Garg, MD, chair, gynecologic oncology, City of Hope Atlanta, Chicago, and Phoenix, discusses treatment approaches for endometrial cancer now and in the near future.

Garg says that when patients are diagnosed with endometrial cancer, surgical management is approached first. This is followed by either adjuvant therapy or observation, depending on the stage of disease at that time point. Garg says, “there’s is a broad spectrum,” of treatment for patients who have successfully undergone surgery.

Other options for endometrial cancer treatment include immunotherapy, which has taken over in the later-line settings, and targeted therapy, which is emerging in the field.

“Immunotherapy has impacted endometrial cancer management. In fact, at the Society of Gynecologic Oncology meeting that was just in March of this year, we had the treatment-altering trials that were presented including the NRG-GY018, and the RUBY trial,” says Garg.

In NRG-GY018 (NCT03914612), a statistically significant and clinically meaningful improvement in progression-free survival (PFS) was shown with pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel in patients with stage III-IV or recurrent endometrial carcinoma regardless of mismatch repair (MMR) status. In RUBY (NCT03981796), dostarlimab (Jemperli) plus carboplatin and paclitaxel in patients with dMMR, microsatellite instability–high (MSI-H) tumors, the agent demonstrated a significant PFS improvement vs placebo.

In terms of targeted therapy for endometrial cancer, Garg explains that the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified 4 important molecular subtypes in 2018 for which novel approaches are being studied in prospective clinical trials.

“What's happening now, is we do the surgery, or we get the pathology specimen, and if there are patients who have the POLE ɛ mutation tumors, and then we know they have a better prognosis, then we may end up de-escalating therapy. Because we're finding out that we may be overtreating some of these patients just because we don't know and we just sort of bucket them all,” Garg says.