Extended follow-up results from the phase III monarchE trial showed that adding the cyclin-dependent kinase inhibitor abemaciclib to standard adjuvant endocrine therapy continued to improve invasive disease–free survival in patients with high-risk, node-positive, early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer. Compared with patients who received endocrine therapy alone, patients who also received abemaciclib had a 28.7% reduced risk of invasive disease. The study was presented by Joyce A. O’Shaughnessy, MD, and colleagues at the 2020 San Antonio Breast Cancer Symposium (Abstract GS1-01).
Joyce A. O’Shaughnessy, MD
Although many patients with HR-positive, HER2-negative early breast cancer will not experience disease recurrence or have distant recurrence with currently available standard therapies, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many just a few years following diagnosis. Earlier results from an interim analysis of the monarchE clinical trial, which is comparing abemaciclib plus adjuvant endocrine therapy with endocrine therapy alone in 5,637 patients with high-risk, node-positive, early-stage, HR-positive, HER2-negative breast cancer, found that abemaciclib plus endocrine therapy demonstrated superior invasive disease–free survival vs endocrine therapy alone (P = .01; hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.60–0.93), with 2-year invasive disease–free survival rates of 92.2% vs 88.7%, respectively. Safety data were consistent with the known safety profile of abemaciclib.
Current Study Methodology
The current study results come from an extended follow-up of the monarchE trial, which analyzed 395 invasive disease–free events with a median follow-up time of 19 months. Following surgery and radiotherapy and/or chemotherapy as indicated, patients in the study were randomly assigned to receive standard-of-care adjuvant endocrine therapy with or without abemaciclib (150 mg twice per day for 2 years). Eligibility criteria for participation in the study included having at least four positive nodes (or having one to three positive nodes in combination with either grade 3 disease); a tumor measuring at least 5 cm; or centrally assessed high Ki-67 status, which is indicative of a fast-growing, aggressive tumor with an increased probability of disease recurrence.
KEY POINTS
- Adding the CDK inhibitor abemaciclib to standard adjuvant endocrine therapy improved invasive disease–free survival in patients with high-risk, node-positive, early-stage, HR-positive, HER2-negative breast cancer.
- Compared with patients who received endocrine therapy alone, patients who also received abemaciclib had a 28.7% reduced risk of invasive disease.
Results
At the time of this analysis, 1,437 patients (25.5%) had completed the 2-year treatment period and 3,281 patients (58.2%) were in the 2-year treatment period. Compared with patients who received endocrine therapy alone, those who also received abemaciclib had a 28.7% reduced risk of invasive disease. The 2-year invasive disease–free survival rate in the combination arm and the endocrine therapy alone arm was 92.3% and 89.3%, respectively. In addition, the researchers observed an improvement in the 2-year distant relapse–free survival rate among patients who received the combination treatment compared with those who received endocrine therapy alone (93.8% vs 90.8%, respectively).
The researchers also evaluated outcomes among 2,498 patients with centrally assessed high Ki-67 status. Among patients in this cohort, those who received the combination treatment had a 30.9% decreased risk of invasive disease compared with those who received endocrine therapy alone. The 2-year invasive disease–free survival rates in the combination arm and the endocrine therapy alone arm were 91.6% and 87.1%, respectively.
Clinical Significance
“Across the spectrum of data for abemaciclib, we have observed a consistent benefit in all subgroups,” said study author Priya Rastogi, MD, Associate Professor at the University of Pittsburgh School of Medicine and Medical Director of the National Surgical Adjuvant Breast and Bowel Project Foundation. “These results may mark a notable treatment advance in the last 2 decades for people living with high-risk, node-positive, HR-positive, HER2-negative early breast cancer. These clinically meaningful results have the potential to change how high-risk, HR-positive, HER2-negative early breast cancer is treated.”
Dr. Rastogi also noted that overall survival data are immature at this time and that additional follow-up is warranted.
Disclosure: The study was sponsored by Eli Lilly and Co.
