Abemaciclib Plus Letrozole Displays Durable Activity in Advanced/Recurrent Endometrioid Endometrial Carcinoma

Abemaciclib (Verzenio) plus letrozole (Femara) showed clinical activity and no new safety signals in patients with advanced or recurrent endometrioid endometrial carcinoma, according to findings from the phase 2 GOG 3039 trial (NCT04393285) presented during the 2026 Society of Gynecologic Oncology Annual Meeting.¹

Among 51 evaluable patients, the primary end point of 6-month progression-free survival (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-naive 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-not estimable) in chemotherapy-naive patients.

“Activity was most pronounced in the chemotherapy-naive population,” lead study author Marilyn Huang, MD, MS, FACOG, head of the UVA Division of Gynecologic Oncology of UVA Health and a professor in the Division of Gynecologic Oncology at the University of Virginia School of Medicine in Charlottesville, 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 GOG 3039, which is 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 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 objective response rate (ORR), PFS, overall survival (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, of whom 51 received treatment. The statistical design incorporated separate thresholds for chemotherapy-naive 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 of 0 (58.8%) or 1 (41.2%) and predominantly grade 1 to 2 disease (90.2%).¹

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

What were the efficacy outcomes with abemaciclib plus letrozole?

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

The median 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.

“Fatigue and diarrhea were the most common [known class effects], 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.

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

Reference

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 SGO Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.