Dr Pothuri on Current Unmet Needs in Recurrent/Advanced Endometrial Cancer

Bhavana Pothuri, MD, professor, Department of Medicine and Department of Obstetrics and Gynecology, New York University (NYU) Grossman School of Medicine; director, Gynecologic Oncology Research, medical director, Clinical Trials Office, director, Gynecologic Oncology Clinical Trials, Perlmutter Cancer Center, NYU Langone Health, discusses ongoing unmet needs for patients with recurrent and advanced endometrial cancer.

Although significant progress has been made in the treatment paradigm for this patient population, challenges remain for patients with recurrent/advanced endometrial cancer, particularly for those with mismatch repair–proficient (pMMR) tumors, Pothuri says.

Pothuri highlights that recent advancements have included the integration of targeted therapies and immunotherapy into earlier treatment settings. In July 2023, the FDA approved dostarlimab-gxly (Jemperli) plus chemotherapy for use in adult patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) primary advanced or recurrent endometrial cancer. Pothuri highlights that this combination could soon be available for patients with pMMR/microsatellite stable (MSS) disease after the FDA granted priority review to a supplemental biologics license application seeking the expanded indication of dostarlimab plus chemotherapy.

Additionally, Pothuri points to the June 2024 FDA approval of pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

Although new therapeutic regimens could help improve outcomes for patients, unmet needs persist, especially for patients within the pMMR subgroup, she says. In this context, Pothuri notes that HER2-directed antibody-drug conjugates (ADCs) could be valuable options for this subset of patients.

Pothuri also notes the efficacy displayed by selinexor (Xpovio) maintenance vs placebo following a response to frontline chemotherapy in patients with TP53 wild-type advanced or recurrent endometrial cancer in the phase 3 SIENDO study (NCT03555422) presented at the 2024 ASCO Annual Meeting. Notably, in a subgroup of patients with TP53 wild-type/pMMR disease, those given selinexor maintenance (n = 47) achieved a median progression-free survival of 39.5 months (95% CI, 19.3–not reached) compared with 4.9 months for those given placebo (n = 23). These types of survival benefits have been rare in this population of patients that is generally difficult to treat, Pothuri concludes.