Dr Pothuri on the Current Treatment Paradigm in Endometrial Cancer

“Especially in the mismatch repair–proficient subset of patients, I think we still have more room to go in the frontline, and I think that's where our HER2 ADCs may be valuable.”

Bhavana Pothuri, MD, gynecologic oncologist, professor, Department of Obstetrics and Gynecology, NYU School of Medicine, discusses new and coming treatments in the endometrial cancer landscape, including immunotherapies and antibody-drug conjugates (ADCs).

In recent years, a lot of progress has been made, particularly in the recurrent and advanced endometrial cancer space, Pothuri begins. Now, there are more novel therapies available in the frontline setting with chemotherapy, including dostarlimab-gxly (Jemperli), she says. In August 2024, the FDA approved dostarlimab plus carboplatin plus paclitaxel, followed by single-agent dostarlimab for the treatment of patients with primary advanced or recurrent endometrial cancer. This approval was an expanded indication based on the July 2023 FDA approval of the combination plus subsequent dostarlimab monotherapy for patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR)—determined by an FDA-approved test—or microsatellite instability high (MSI-H). Although these changes have made strides in the endometrial cancer treatment paradigm, Pothuri notes that there is still work to be done, especially for patients with mismatch repair–proficient (pMMR) disease.

Other treatments, such as selinexor (Xpovio), have also shown promise in efficacy in the maintenance setting following chemotherapy, based on data from the phase 3 SIENDO trial (NCT03555422), Pothuri explains. As of April 1, 2024, the median progression-free survival for patients with TP53 wild-type disease was 28.4 months vs 5.2 months in the selinexor and placebo arms, respectively. Pothuri emphasizes that these results are not often seen in patients from the pMMR subgroups; therefore, it’s crucial to have better access to a new therapy that could serve as another frontline maintenance treatment.

Furthermore, ADCs could also pose a potential treatment option in the second line, specifically if more immunotherapies move into the frontline, Pothuri says. ADCs of significance include folate receptor alpha (FRα)–targeting ADCs and the HER2–directed ADC, fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), she notes.

Endometrial cancer historically was a disease that only had 1 or 2 effective treatments, Pothuri explains. However, now there are treatment options in the fourth- and fifth-line settings because of ongoing trials and FDA approvals, along with many unmet needs that require addressing, she concludes.