Results of a planned interim overall survival analysis of the phase III monarchE trial offer further support for the addition of abemaciclib to adjuvant endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive, high-risk breast cancer, according to Stephen R.D. Johnston, MD, PhD, of the Royal Marsden NHS Foundation Trust, who reported the data at the 2022 San Antonio Breast Cancer Symposium (Abstract GS1-09).

“In the monarchE trial, with additional follow-up, the benefit of adjuvant abemaciclib deepened in magnitude, with an increase in absolute invasive disease–free survival and distant recurrence–free survival benefit at 4 years, as compared to the 2-year and 3-year rates,” Dr. Johnston said.

At the 4-year time point, the difference in invasive disease–free survival favoring abemaciclib was 6.4%, compared with a 4.8% difference observed at 3 years and a 2.8% difference at 2 years. The results were simultaneously published in The Lancet Oncology.

Stephen R.D. Johnston, MD, PhD

“Benefit was demonstrated across all prespecified subgroups. Ki-67 remained prognostic, but the abemaciclib benefit was similar regardless of Ki-67 index,” Dr. Johnston said.

While the overall survival data remain immature at this time, fewer deaths were observed with abemaciclib plus endocrine therapy compared to endocrine therapy alone, he added.

Study Details

The randomized open-label phase III monarchE trial enrolled 5,637 patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer deemed at high risk based on clinical pathologic features (cohort 1, 91% of patients) or based on Ki-67 ≥ 20% (cohort 2, 9% of patients). While the study could include untreated patients, Dr. Johnston said, “It’s important to note that 95% of patients in the trial received either neoadjuvant or adjuvant chemotherapy.”

Patients received 2 years of treatment with endocrine therapy (aromatase inhibitor of tamoxifen) alone or with abemaciclib at 150 mg twice daily. The primary objective was invasive disease–free survival.

In the previously reported primary analysis, published in the Journal of Clinical Oncology, adjuvant abemaciclib plus endocrine therapy demonstrated a significant improvement in both invasive disease–free survival and distant recurrence–free survival. The current preplanned analysis was conducted 2 years later and represents a 4-year landmark analysis. Patients were followed a median of 4 years and are all now off treatment with abemaciclib.

Efficacy of Abemaciclib/Endocrine Therapy at 4 Years

After 4 years, invasive disease–free survival was 85.8% with abemaciclib/endocrine therapy vs 79.4% with endocrine therapy alone (hazard ratio [HR] = 0.664, P < .0001). Invasive disease–free survival rates were previously reported to be 92.7% vs 89.9%, respectively, at 2 years, and 89.2% vs 84.4% at 3 years.

“For the updated efficacy results for the primary outcome of invasive disease–free survival in the intent-to-treat population, you can see that with further follow-up, the Kaplan-Meier curves continue to separate beyond completion of the 2 years of treatment, suggesting a potential carryover effect,” Dr. Johnston said. He also noted that the benefit of abemaciclib was consistent across all prespecified subgroups.

A distant relapse–free survival benefit also persisted beyond the completion of abemaciclib. At 4 years, these rates were 88.4% with abemaciclib/endocrine therapy vs 82.5% with endocrine therapy alone (HR = 0.659, P < .0001). This 5.9% difference—representing a 34.1% reduction in risk—was an increase over the rates of 2.5% at 2 years and 4.1% at 3 years, Dr. Johnston noted.

For both invasive disease–free survival and distant relapse–free survival, the hazard ratios have become more favorable over time, further supporting the potential of a carryover effect, he said.  

“Overall survival data remain immature, but we can see a numerical difference, with 157 deaths in the abemaciclib arm vs 173 in the endocrine therapy alone arm,” he said. Twice as many patients have developed metastatic disease: 249 with endocrine therapy alone and 125 with abemaciclib/endocrine therapy.  

Efficacy Outcomes by Cohort

Hazard ratios were determined for the two cohorts. For cohort 1 (high risk as determined by clinicopathologic features), and for cohort 2 (high risk as determined by Ki-67), the hazard ratios were 0.653 and 0.773, respectively, for invasive disease–free survival. For distant relapse–free survival, they were 0.652 for cohort 1 and 0.764 for cohort 2.

In cohort 1, pretreatment biopsies analyzed for Ki-67, a marker of cell proliferation, showed this to be prognostic of outcomes but not predictive of abemaciclib benefit.

“Similar abemaciclib treatment effects were observed regardless of Ki-67 index,” Dr. Johnston said.

The safety data was consistent with previous analyses, with no new safety signals emerging.

Disclosure: Dr. Johnston reported financial disclosures for Pfizer, Novartis, Eisai, AstraZeneca, Roche, Eli Lilly, and Puma Biotechnology.