Abemaciclib/Letrozole Elicits Activity in Recurrent Endometrioid Endometrial Cancer

Among patients with advanced or recurrent endometrioid endometrial carcinoma, the combination of abemaciclib (Verzenio) and letrozole achieved antitumor activity and disease control. These data from the phase 2 GOG 3039 trial (NCT04393285) were presented at the 2026 Society of Gynecologic Oncology Annual Meeting on Women's Cancer (SGO).¹

Data showed that among 51 evaluable patients, the primary end point of 6-month PFS was 56.9%. When stratified by prior systemic exposure, patients who had received prior chemotherapy had a 6-month PFS rate of 46.7%, whereas chemotherapy-naïve patients achieved a rate of 71.4%.

Overall, the median PFS was 9.5 months (95% CI, 5.5-12.7). The median PFS was 6.9 months (95% CI, 2.4-11.1) in previously treated patients compared with 12.7 months (95% CI, 6.1-NE) in chemotherapy-naïve patients.

“Activity was most pronounced in the chemotherapy-naïve population,” lead study author Marilyn Huang, MD, MS, FACOG, head of the UVA Division of Gynecologic Oncologyof UVA Health, professor in the Division of Gynecologic Oncology at University of Virginia of School of Medicine, said during an oral presentation of the data.

Hormone receptor–positive endometrial cancer remains an area of active investigation for endocrine-based combination strategies, particularly in the recurrent setting where responses to hormonal therapy alone are often modest and not durable.

At the meeting, Huang presented findings from the phase 2 GOG 3039 trial evaluating abemaciclib plus letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma.

“Endometrial cancer has a strong biologic rationale for endocrine-based therapy…however, responses to hormonal therapy alone are modest and often not durable,” Huang said during the oral presentation.

How was the GOG 3039 trial designed?

GOG 3039 was a multicenter, open-label, single-arm phase 2 trial designed with a 2-stage structure that enrolled patients with advanced (FIGO 2014 stage III/IV) or recurrent endometrioid endometrial carcinoma not amenable to curative surgery or radiation.

Patients received abemaciclib 150 mg orally twice daily plus letrozole 2.5 mg once daily in 28-day cycles. The primary end point was 6-month PFS; secondary end points included ORR, PFS, OS, and safety.

“We conducted GOG 3039…to evaluate this combination in an endometrioid population with measurable disease and good performance status,” Huang explained.

The trial enrolled 53 patients across 19 sites, with 51 receiving treatment. The statistical design incorporated separate thresholds for chemotherapy-naïve and previously treated cohorts to account for expected differences in outcomes.

What were the baseline patient characteristics of the GOG 3039 trial?

The median age was 65 years (range, 29-85). Patients had an ECOG performance status 0 (58.8%) or 1 (41.2%) and predominantly grade 1-2 disease (90.2%).¹

Most patients (58.8%) had received prior chemotherapy. Overall, 62.7% had received 1 to 2 prior lines of therapy. Two patients received single-agent pembrolizumab (Keytruda).

What were the efficacy outcomes with abemaciclib plus letrozole?

Furthermore, the regimen achieved an objective response rate (ORR) of 39.2% (95% CI, 25.8%-53.9%), including complete responses (CRs) in 9.8% and partial responses (PRs) in 29.4%. Stable disease (SD) was observed in 31.4% of patients, translating to a clinical benefit rate (CBR) of 70.6%. Progressive disease (PD) occurred in 17.6%, and 11.8% of responses were indeterminate.

The median overall survival (OS) was not reached at the time of analysis. Kaplan-Meier estimates demonstrated sustained separation of the PFS curve beyond 6 months.¹

Additional data showcased that a subset of patients experienced prolonged benefit. “The curve plateaus at approximately 27% beyond 20 months…highlighting a subset with durable disease control,” Huang noted.

What was the safety profile of abemaciclib plus letrozole?

The safety profile was consistent with known CDK4/6 inhibitor class effects, with no new safety signals identified.

“The toxicity profile was consistent with the known class effects…fatigue and diarrhea were the most common, with relatively low rates of grade 3 or higher toxicity,” Huang said.

The most common all-grade adverse events included fatigue (68.6%), diarrhea (66.7%), increased creatinine (41.2%), anemia (37.3%), and neutropenia (37.3%).

Grade 3 or higher adverse events included neutropenia (15.7%), anemia (11.8%), and fatigue (11.8%). Additional grade 3 toxicities included diarrhea and hepatic enzyme elevations

“There were no new or unexpected safety signals and no treatment-related deaths,” Huang noted.

Editor’s Note: Huang disclosed advisory roles with AbbVie, AstraZeneca, Merck, Natera, Pfizer, ImmunoGen, and GSK; participation on a scientific advisory council for Pfizer; and consulting for the Association of Cancer Care Centers.

Reference

1. Huang M, Huang G, Sill M, et al. Phase II study of abemaciclib plus letrozole in advanced or recurrent endometrioid endometrial carcinoma: a GOG Partners trial (GOG 3039). Presented at: 2026 Society of Gynecologic Oncology Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.