Abemaciclib-Based Treatments for HR+, HER2– Advanced Breast Cancer | Breast Cancers Today

Updated results from the phase 3 postMONARCH trial offered further support for the efficacy and tolerability of abemaciclib plus fulvestrant for HR-positive, HER2-negative advanced breast cancer after progression on a CDK4/6 inhibitor and endocrine therapy. While the use of CDK4/6 inhibitors in combination with endocrine therapy in the first line has improved outcomes for patients with HR-positive, HER2-negative advanced breast cancer, “disease progression occurs in almost all patients,” wrote Kevin Kalinsky, MD, from Winship Cancer Institute at Emory University in Atlanta, Georgia, and colleagues.

There is an unmet need for safe, effective therapies that can follow first-line CDK4/6 inhibitors plus endocrine therapy and delay the need for chemotherapy or antibody-drug conjugates. Abemaciclib is an oral CDK4/6 inhibitor with greater selectivity for CDK4 than CDK6, allowing continuous dosing.

Previous trials have shown that abemaciclib plus endocrine therapy improved the progression-free survival (PFS) and overall survival (OS) for patients with advanced breast cancer. In postMONARCH, a global, randomly assigned, double-blind, placebo-controlled, phase 3 trial, 368 patients with HR-positive, HER2-negative advanced breast cancer who had progressed on CDK4/6 inhibition plus endocrine therapy were included.

Patients were randomly assigned to receive either abemaciclib plus fulvestrant (n = 182) or placebo plus fulvestrant (n = 186). Previously, postMONARCH data demonstrated a statistically significant improvement in PFS with abemaciclib plus fulvestrant (median PFS, 6.0 months; 6-month PFS rate, 50%) versus placebo plus fulvestrant (median PFS, 5.3 months; 6-month PFS rate, 37%).

Now, the study authors report on the final overall survival analysis, which was prespecified at 200 OS events with a hazard ratio (HR) boundary of 0.753. The median follow-up was duration was approximately 37 months. The median OS was 32.1 months in the abemaciclib-fulvestrant arm versus 24.6 months in the placebo-fulvestrant arm (HR, 0.80; P =0.11).

Although this did not reach statistical significance, there was a numerical trend favoring abemaciclib-fulvestrant, with a 20% reduction in the risk of death. Likewise, the median OS was numerically longer with abemaciclib-fuvestrant, at 32.1 months, when compared to placebo-fulvestrant, 24.6 months.

The difference in OS was consistent across subgroups. Dr. Kalinsky and colleagues determined, “The totality of evidence supports the consideration of abemaciclib-based treatment [for] patients with hormone receptor-positive, HER2-negative ABC [advanced breast cancer] after disease progression on CDK4/6i [inhibitor] plus ET [endocrine therapy].”