As reported in the Journal of Clinical Oncology by Stephen R.D. Johnston, MD, PhD, and colleagues, the phase III monarchE trial has shown that adjuvant abemaciclib plus endocrine therapy significantly improved invasive disease–free survival vs endocrine therapy alone in patients with hormone receptor (HR)-positive, HER2-negative, node-positive early breast cancer who are at high risk for disease recurrence.

As stated by the investigators, “Many patients with HR-positive, HER2-negative early breast cancer will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients.”

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 abemaciclib at 150 mg twice daily for 2 years plus standard-of-care endocrine therapy (n = 2,808) or endocrine therapy alone (n = 2,829). Most patients had received prior radiotherapy and adjuvant/neoadjuvant chemotherapy.

Patients had to have four or more positive nodes, or one to three positive nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%. The primary endpoint was invasive disease–free survival in the intent-to-treat population.

Invasive Disease–Free Survival

At the second preplanned efficacy interim analysis, with data cutoff in March 2020, median follow-up was approximately 15.5 months in each group. A total of 323 patients had invasive disease–free survival events, including 136 (4.8%) in the abemaciclib group and 187 (6.6%) in the control group. The hazard ratio (HR) for the abemaciclib vs control group was 0.75 (95% confidence interval [CI] = 0.60–0.93, P = .01), with 2-year rates of 92.2% vs 88.7%.

Most invasive disease–free survival events were distant recurrences, observed in 87 patients in the abemaciclib group and 138 in the control group. The abemaciclib group had significantly improved distant metastasis–free survival (HR = 0.72, 95% CI = 0.56–0.92, nominal P = .01), with 2-year rates of 93.6% vs 90.3%. Overall survival data were immature at the time of analysis, with death occurring in 1.4% vs 1.3% of patients.

Adverse Events

The most common adverse events of any grade were diarrhea, neutropenia, and fatigue in the abemaciclib group, and arthralgia, hot flush, and fatigue in the control group. Grade ≥ 3 adverse events occurred in 45.9% vs 12.9% of patients. Serious adverse events occurred in 12.3% vs 7.2% of patients, with the most common being pneumonia (0.8% vs 0.5%).

Venous thromboembolic events occurred in 2.3% vs 0.5% of patients, including pulmonary embolism in 0.9% vs 0.1%. Interstitial lung disease occurred in 2.7% vs 1.2% of patients. Adverse events led to death in 11 patients in the abemaciclib group (with 2 [diarrhea and pneumonitis] considered possibly related to treatment) and 7 patients in the control group.

The investigators concluded: “Abemaciclib when combined with endocrine therapy is the first CDK4/6 inhibitor to demonstrate a significant improvement in invasive disease–free survival in patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of early recurrence.”

Dr. Johnston, of the Royal Marsden NHS Foundation Trust, London, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.org.