Initial Treatment With CDK4/6 Inhibitor and Aromatase Inhibitor for Advanced Breast Cancer

Key Points

  • In initial treatment of women with advanced breast cancer, the addition of abemaciclib vs placebo to a nonsteroidal aromatase inhibitor significantly improved progression-free survival.
  • Median progression-free survival was not reached vs 14.7 months.

As reported in the Journal of Clinical Oncology by Goetz et al, an interim analysis in the phase III MONARCH 3 trial has shown a significant progression-free survival benefit with the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib (Verzenio) to a nonsteroidal aromatase inhibitor as initial treatment of advanced hormone receptor–positive, HER2-negative breast cancer.

Study Details

In the double-blind trial, 493 postmenopausal women from 158 sites in 22 countries with no prior systemic therapy in the advanced setting were randomized 2:1 between November 2014 and November 2015 to receive abemaciclib at 150 mg twice daily (n = 328) or placebo (n = 165) plus either 1 mg of anastrozole or 2.5 mg of letrozole daily. Overall, 79% of patients received letrozole. The primary endpoint was investigator-assessed progression-free survival. A planned interim analysis was performed after 189 events.

Patents had a median age of 63 years, and 57% (abemaciclib group) to 62% were white, and 27% to 31% (abemaciclib group) were Asian. Among all patients, 97% had metastatic disease, 53% had visceral metastases, 40% had de novo metastases, and 47% had received neoadjuvant or adjuvant endocrine therapy (including aromatase inhibitor therapy in 27%).

Progression-Free Survival

At an interim analysis, performed after 194 progression-free survival events, the median follow-up was 17.8 months. Median progression-free was not reached in the abemaciclib group vs 14.7 months in the placebo group (hazard ratio [HR] = 0.54, P = .000021). A benefit of abemaciclib was observed across specified subgroups; the hazard ratio was lower among Asian patients (HR = 0.30, 95% confidence interval [CI] = 0.17–0.52) than among white patients (HR = 0.69, 95% CI = 0.48–0.99).

Objective response rates were 48.2% vs 34.5% (P = .002); the median duration of response was not reached in the abemaciclib group vs 14.1 months in the placebo group. Among the approximately 80% of patients with measurable disease, response rates were 59.2% vs 43.8% (P = .004). A final overall survival analysis will occur after 315 deaths.

Adverse Events

Diarrhea was the most common adverse event of any grade in the abemaciclib group (81%; 45% grade 1). Grade 3 or 4 adverse events occurred in 55% of the abemaciclib group vs 22% of the placebo group, with the most common in the abemaciclib group being neutropenia (21.1% vs 1.2%), diarrhea (9.5% vs 1.2%), and leukopenia (7.6% vs 0.6%). Serious adverse events occurred in 27.5% vs 14.9%, with the most common in the abemaciclib group being lung infection (2.8% vs 0%).

The investigators concluded: “Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with [hormone receptor–]positive, HER2-negative advanced breast cancer.”

The study was funded by Eli Lilly.

Matthew P. Goetz, MD, of the Mayo Clinic, Rochester, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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