Latest treatment option in uterine cancer

According to the latest report from the US Centers for Disease Control and Prevention (CDC), while the incidence of almost all cancers has declined over the past two decades, the incidence of uterine cancer has risen. More than 90% of uterine cancers occur in the endometrium and are called endometrial cancer. Early endometrial cancer has a good prognosis, with a five-year relative survival rate estimated between 80% and 90%. Its most typical symptoms are abnormal bleeding before and after menopause, weight loss, and pelvic pain. However, for advanced metastatic patients, treatment options remain very limited.

The US FDA recently approved the PD-1 inhibitor Keytruda (pembrolizumab) in combination with the oral tyrosine kinase inhibitor Lenvima (lenvatinib) to treat patients with specific advanced endometrial cancer — notably, patients who do not require high microsatellite instability (MSI-H) or mismatch repair defect (dMMR) types. This approval applies to patients whose disease continues to progress after early systemic therapy and who cannot undergo curative surgery or radiotherapy. The accelerated approval was granted simultaneously in the United States, Australia, and Canada, based on a study of 94 patients in which the overall response rate was 38.3%, including a 10.6% complete response rate. Since at least 75% of endometrial cancer patients are not of the MSI-H or dMMR type, this combination therapy brings new hope to the majority of those affected.

Several promising clinical trials are currently advancing the treatment of endometrial cancer, each targeting a specific limitation of existing therapies. A trial led by Konstantinopoulos is combining the immune checkpoint inhibitor avelumab with the PARP inhibitor talazoparib to explore whether this pairing can improve outcomes in patients with the more common microsatellite stable (MSS) form of the disease, where immunotherapy alone has shown little activity. A separate trial led by Jennifer Veneris is testing the combination of pembrolizumab with mirvetuximab, also in MSS endometrial cancer patients, with mirvetuximab delivering drug molecules directly to rapidly dividing cancer cells.

Another trial led by Konstantinopoulos is testing the combination of abemaciclib, LY3023414, and hormone therapy to address resistance to hormone blocking treatment — a common challenge given that 70% to 90% of endometrial cancers are estrogen-driven and eventually relapse after hormone therapy. A fourth trial, led by Joyce Liu at Dana-Farber, is using AZD1775 specifically for patients with high-grade serous uterine cancer, an aggressive subtype that accounts for 10–15% of endometrial cancers and typically recurs after standard treatment.

Finally, the Phase I/II GARNET trial results for dostarlimab (TSR-042), a humanized anti-PD-1 monoclonal antibody, showed an overall response rate of nearly 30% in patients with relapsed or advanced endometrial cancer, with response rates of 48.8% in MSI-H patients and 20.3% in MSS patients. Notably, 84% of responding patients were still receiving treatment at the time of reporting, and further Phase III studies combining dostarlimab with chemotherapy as first-line treatment are planned, offering continued promise for this patient population.