Abemaciclib plus letrozole effective in treating recurrent ER-positive endometrial cancer

Results from a phase 2 study showed that abemaciclib in combination with letrozole shrunk or stabilized tumors in 75% of patients with recurrent or persistent estrogen receptor-positive, or ER-positive, endometrial cancer.

“For patients with ER-positive endometrial cancer, hormonal/endocrine therapy is used as an alternative option after progression through chemotherapy and immunotherapy or as an alternative, less toxic option for those with more indolent or minimally symptomatic disease,” Panagiotis A. Konstantinopoulos, MD, PhD, director of gynecologic oncology translational research and physician at Dana-Farber Cancer Institute, told Healio. “However, responses to endocrine therapy are typically modest and relatively brief in duration (median progression-free survival of about 3 months), with only a minority of patients deriving benefit for extended period of time.

“In prior studies, aromatase inhibitor monotherapy exhibits limited activity in endometrial cancer, with response rates for both letrozole and anastrozole below 10%,” Konstantinopoulos, also an associate professor of medicine at Harvard Medical School, said. “For this reason, development of novel strategies to improve the efficacy of endocrine therapy represents an unmet need and an area of active investigation in endometrial cancer.”

In the study, presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer, the researchers evaluated the efficacy of 150 mg of abemaciclib twice daily and 2.5 mg of letrozole daily — a targeted drug and an aromatase inhibitor, respectively — in 28 patients who had recurrent ER-positive endometrial cancer, according to the abstract. They analyzed the objective response rate and the progression-free survival rate at 6 months.

At a median follow-up of 12.5 months, 75% of patients’ tumors had become smaller or stabilized, and about 30% had their tumors shrink by at least 30%, according to a press release from the Dana-Farber Cancer Institute.

Progression-free survival at 6 months was 55.6% (95% CI, 35.1%-72%), with a median progression-free survival of 9.1 months (95% CI, 3.5-16.5).

The most common toxicities were neutropenia in five patients and anemia in three patients; two patients discontinued treatment due to toxicity. There was at least one dose reduction of abemaciclib in 16 patients.

“Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER-positive endometrial cancer and may an effective endocrine therapy approach for patients with recurrent ER-positive endometrioid endometrial cancer,” Konstantinopoulos told Healio.

Moving forward, the researchers will examine genomic mutations related to endocrine resistance.

“Additional planned future correlative work from our study includes assessing genomic alterations associated with endocrine resistance (such as ESR1 and PIK3CA mutations) on circulating tumor DNA from serial blood specimens collected from patients at baseline (prior to initiation of protocol therapy), at C2D1, at the time of response and at the time of progression,” Konstantinopoulos said.

Reference:

• Drug combination shows effectiveness in patients with recurrent ER-positive endometrial cancer. https://www.eurekalert.org/news-releases/946648. Published March 19, 2022. Accessed March 21, 2022.