Dr Moore on the Evolution of Treatment Strategies for Advanced Endometrial Cancer

“The treatment paradigm for advanced and recurrent endometrial cancer is rapidly evolving [and] will likely be different, [possibly] in 6 to 12 months, which is exciting for patients.”

Kathleen N. Moore, MD, MS, associate director of Clinical Research at the Stephenson Cancer Center, as well as director of the Oklahoma TSET Phase I Program and a professor in the Section of Gynecologic Oncology at The University of Oklahoma Health College of Medicine, discusses the current treatment paradigm for patients with advanced recurrent endometrial cancer.

The treatment paradigm for advanced and recurrent endometrial cancer is undergoing rapid transformation, and current treatment recommendations are likely to continue evolving significantly within the next few months, Moore began. This evolution is noteworthy given that, for decades, patients with advanced or recurrent disease had extremely limited therapeutic options, she said.

For many years, the standard of care (SOC) in the first-line metastatic setting was platinum-based chemotherapy, most commonly the combination of paclitaxel and carboplatin or cisplatin, Moore explained. These regimens provide modest efficacy, with objective response rates of approximately 50% to 60%, she stated. However, these responses are typically short-lived, with recurrences expected within the first year of treatment, she noted. Until the introduction of targeted therapies, such as the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda), therapeutic options beyond frontline chemotherapy were largely ineffective, she reported. Cytotoxic chemotherapy alone demonstrated minimal activity in the recurrent setting, and patients frequently succumbed to their disease, highlighting the historically poor prognosis of advanced endometrial cancer, according to Moore.

A recent paradigm shift occurred with the presentation and subsequent publication of data from pivotal phase 3 clinical trials, Moore emphasized. Each of these studies had slightly different designs, but all investigated incorporating immune checkpoint inhibitors into chemotherapy backbones with subsequent maintenance therapy, she continued. These advances represent the first meaningful integration of molecular characterization from The Cancer Genome Atlas into frontline endometrial cancer management, she added. Although the established molecular subgroups of endometrial cancer, including POLE mutated, mismatch repair deficient (dMMR), and mismatch repair proficient, have been recognized for more than a decade, their clinical utility in guiding initial treatment has only now been realized, she detailed.

Pivotal trial data have been most transformative for patients with dMMR or microsatellite instability–high (MSI-H) tumors, Moore said. Although approximately 30% of these patients continue to experience disease progression within the first year, most of those who remain progression free experience durable outcomes, she explained. Additionally, emerging overall survival data suggest the possibility of long-term disease-free survival and, for some patients, even cure, she noted. As a result, the current SOC for patients with advanced or recurrent dMMR or MSI-H endometrial cancer is now combination therapy with platinum-based chemotherapy plus an immune checkpoint inhibitor, followed by checkpoint inhibitor maintenance, she concluded.