Dr Konstantinopoulos on the Safety of Letrozole, Abemaciclib, and Metformin in ER+ Recurrent Endometrial Cancer

"We were very happy that the regimen was generally very well tolerated without any new safety signals, compared to what we have seen with previous CDK 4/6 inhibitor studies and hormonal therapy."

Panagiotis A. Konstantinopoulos, MD, PhD, director of the Mellen and Eisenson Family Center for BRCA and Related Genes, director of Translational Research in the Division of Gynecologic Oncology, and the Velma Eisenson Endowed Chair for Clinical and Translational Research at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, discussed safety findings from the phase 2 RESOLVE trial (NCT03675893) evaluating the combination of letrozole, abemaciclib (Verzenio), and metformin in patients with estrogen receptor (ER)–positive, recurrent endometrial cancer.

Results presented at the 2025 SGO Annual Meeting on Women’s Cancer showed that the addition of metformin to the combination of letrozole and abemaciclib was feasible and well tolerated with a manageable safety profile consistent with previously reported outcomes for CDK4/6 inhibitors combined with endocrine therapy, Konstantinopoulos reported. No new or unexpected treatment-related adverse effects (TRAEs) were observed with the addition of metformin, he noted.

Among 25 patients enrolled in the trial, the most common grade 3 TRAEs were neutropenia (24%), fatigue (16%), and anemia (8%). No grade 4 or grade 5 toxicities occurred, and no patients discontinued treatment due to toxicity, Konstantinopoulos emphasized. These results suggested that the triplet regimen could be administered safely without requiring dose-limiting modifications or triggering treatment discontinuation.

Konstantinopoulos noted that these toxicity rates were comparable to prior trials, such as a phase 2 study (NCT03675893) of letrozole plus abemaciclib without metformin.

Moreover, the absence of grade 4 or higher toxicities represents a reassuring safety signal for patients with limited treatment options in the recurrent endometrial cancer setting, he concluded.