As reported in The Lancet Oncology by Stephen R.D. Johnston, MD, PhD, and colleagues, an interim analysis of overall survival in the phase III monarchE trial has shown no significant benefit with the addition of adjuvant abemaciclib to endocrine therapy in patients with hormone receptor–positive, HER2-negative, node-positive, high-risk early breast cancer. The updated analysis showed continued benefits in invasive disease–free survival and distant relapse–free survival.
The trial supported the October 2021 approval of abemaciclib in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of patients with hormone receptor–positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence who had a Ki-67 score of ≥ 20%, based on improved invasive disease–free survival in the subgroup of patients with a Ki-67 score of ≥ 20%.
Stephen R.D. Johnston, MD, PhD
Study Details
In the open-label trial, 5,637 patients from sites in 38 countries were randomly assigned between July 2017 and August 2019 to receive physician’s choice of standard-of-care endocrine therapy for up to 10 years with (n = 2,808) or without (n = 2,829) abemaciclib at 150 mg twice daily for 2 years. The 2021 approval was based on findings in 1,017 patients in the abemaciclib group and 986 in the control group with a Ki-67 score of ≥ 20%.
The current prespecified overall survival interim analysis was planned to occur 2 years after the primary outcome analysis for invasive disease–free survival. All efficacy outcomes in the current report were assessed in the total intention-to-treat (ITT) population.
Key Findings
At data cutoff for overall survival interim analysis (in July 2022), median follow-up for the total ITT population was 42 months (interquartile range = 37–47 months).
Overall survival data were not mature. Death occurred in 157 patients (5.6%) in the abemaciclib group vs 173 patients (6.1%) in the control group (hazard ratio [HR] = 0.929, 95% confidence interval [CI] = 0.748–1.153, P = .50). Death was due to breast cancer in 118 patients (4.2%) vs 139 patients (4.9%).
Invasive disease–free survival events were observed in 336 patients (12.0%) in the abemaciclib group vs 499 patients (17.6%) in the control group (HR = 0.664, 95% CI = 0.578–0.762, nominal P < .0001). Estimated rates at 4 years were 85.8% vs 79.4%. The absolute difference at 4 years was 6.4%, compared with 2.8% at 2 years.
Distant relapse–free survival events were observed in 281 patients (10.0%) in the abemaciclib group vs 421 patients (14.9%) in the control group (HR = 0.659, 95% CI = 0.567–0.767, nominal P < .0001). Estimated rates at 4 years were 88.4% vs 82.5%. The absolute difference at 4 years was 5.9%, compared with 2.5% at 2 years.
The most common grade 3 or 4 adverse events in the abemaciclib group were neutropenia (19.6% vs 0.9% in control group), leukopenia (11.4% vs 0.4%), and diarrhea (7.8% vs 0.2%). Serious adverse events occurred in 15.5% vs 9.1% of patients. Treatment-related death occurred in two patients in the abemaciclib group (due to diarrhea and pneumonitis, respectively) and no patients in the control group.
The investigators concluded, “Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk [hormone receptor–]positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients.”
Dr. Johnston, of The Royal Marsden NHS Foundation Trust, London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Eli Lilly. For full disclosures of the study authors, visit thelancet.com.
