June 1, 2024
By Catlin Nalley
Phase II data demonstrated durable responses among patients with advanced or recurrent endometrial cancer who underwent treatment with a combination of abemaciclib and fulvestrant. These findings were recently presented by Angela Green, MD, Gynecologic Oncologist at Memorial Sloan Kettering Cancer Center, during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5511).
“Inhibition of the cyclin D-Cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy,” according to Green and colleagues. “Elevated CDK4 expression is observed in 34-77 percent of endometrioid endometrial cancers and is an early event of neoplastic transformation.
“Responses to endocrine monotherapy in advanced or recurrent endometrial cancer are suboptimal and short-lived,” they continued. “We hypothesized that CDK4/6 inhibition with abemaciclib combined with fulvestrant is a promising strategy to improve outcomes with endocrine therapy in patients with advanced or recurrent hormone receptor-positive endometrial cancer.”
In this investigator-initiated, open-label, single-arm, Phase II study, eligible patients included adults (≥18 years) with advanced or recurrent endometrial cancer. Other eligibility criteria were estrogen receptor or progesterone receptor expression ≥ 1 percent by immunohistochemistry, measurable disease, no more than two prior lines of chemotherapy, and no more than one prior line of hormonal therapy. All histologies could be included except carcinosarcoma, according to the study authors who noted that mixed histologies required ≥95 percent endometrioid component.
“Patients received fulvestrant 500 mg intramuscularly monthly with an initial 2-week loading dose and abemaciclib 150 mg orally twice daily until disease progression or prohibitive toxicity,” Green and team outlined. The primary endpoint was objective response rate by Response Evaluation Criteria in Solid Tumors v1.1.
As of the data cutoff of October 7, 2023, 27 patients initiated protocol therapy and 25 were evaluated for efficacy, according to the study abstract. Twenty-four (89%) had tumors with endometrioid histology, nine patients (33%) had prior hormonal therapy, and 26 patients (96%) had at least one prior line of chemotherapy, the study authors reported.
“Eleven patients achieved a partial response resulting in an objective response rate of 44 percent (90% CI: 27.0% to 62.1%),” Green and colleagues stated. “The median duration of response, among patients that experienced a response, was 15.6 months (90% CI, 7.2-nonestimable [NE]).
“All responses were in Grade 1 or 2 endometrioid endometrial cancers,” they explained. “Ten out of 11 responses (91%) were in patients with copy number low/no specific molecular profile endometrial cancers, while one response (9%) was in a patient with microsatellite instability-high endometrial cancer. The median progression-free survival was 9 months (90% CI: 1.8 to 20.4) and median overall survival was 37.8 months (90% CI: 16.3 to NE).”
In terms of safety, the most common Grade 3 or higher treatment-related adverse events were neutropenia (22%) and anemia (19%).
In conclusion, this Phase II study of fulvestrant plus abemaciclib in hormone receptor-positive advanced or recurrent endometrial cancer showed that this therapeutic approach has promising activity, leading to durable responses in the study population. Further analysis is planned in a Phase III clinical trial.
Catlin Nalley is a contributing writer.