By Kate O’Rourke
Compared to endocrine therapy alone, abemaciclib plus endocrine therapy improves invasive disease-free survival (IDFS) in patients with high-risk, node-positive, early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer, according to extended follow-up data from the phase 3 monarchE trial presented at the 2020 San Antonio Breast Cancer Symposium.
The results come from an analysis of 395 invasive disease-free events with a median follow-up time of 19 months that revealed that those who received abemaciclib had a 28.7% reduced risk of invasive disease (P=0.0009).
In the trial, researchers randomized patients following surgery, and radiotherapy and/or chemotherapy as indicated, to receive endocrine therapy with or without abemaciclib (Abstract GS1-01). At the time of analysis, 1,437 patients had completed the 2-year treatment period and 3,281 patients were in the 2-year treatment period. Eligibility criteria included having at least four positive nodes, or having one to three positive nodes in combination with either grade 3 disease, a tumor of at least 5 cm, or centrally assessed high Ki-67 status (at least 20% positivity in tumor cells).
The 2-year IDFS rate was 92.3% in those who received abemaciclib and 89.3% in those who received abemaciclib plus endocrine therapy.
The 2-year distant relapse-free survival rate was also improved in the abemaciclib cohort (93.8% vs. 90.8%). The benefit of abemaciclib was consistent in all subgroups, and safety data were consistent with the known safety profile of the drug.
“Abemaciclib in combination with endocrine therapy is the first CDK4/6 inhibitor to demonstrate efficacy and tolerability for patients with hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer,” said Priya Rastogi, MD, associate professor at the University of Pittsburgh Department of Medicine and medical director of the National Surgical Adjuvant Breast and Bowel Project Foundation, who presented the study.
Among 2,498 patients with centrally assessed high Ki-67 status, patients who received abemaciclib had a 30.9% decreased risk of invasive disease, compared with those who received endocrine therapy alone (P=0.0111). In this cohort, the 2-year IDFS rates were higher in patients who received abemaciclib (91.6% vs. 87.1%).
In a previous interim analysis of the monarchE trial, after a median follow-up of 15.5 months and 323 invasive disease-free events, the addition of abemaciclib to endocrine therapy reduced the risk of invasive disease by 25%.
The current findings are “very encouraging,” especially in the subgroup of tumors with high proliferation, said C. Kent Osborne, MD, founding director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine in Houston. But he said caution is needed in interpreting the findings given the short follow-up, that ER-positive disease is known for its persistent recurrence rate even past 10 years, and that CDK4/6 inhibitors block cell proliferation rather than killing cells.
“An important question remains: will the invasive disease-free survival curves come together when the drug is stopped?” Dr. Osborne said.