FDA D.I.S.C.O. Burst Edition: FDA approval of Verzenio (abemaciclib) with endocrine therapy for patients with HR-positive, HER2-negative, node-positive, early breast cancer

FDA approval (March 3, 2023): abemaciclib + endocrine therapy in high-risk early breast cancer

The FDA approved abemaciclib (Verzenio) in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence.

High-risk was defined as either:

• ≥4 pathologic axillary lymph nodes, or
• 1–3 pathologic axillary lymph nodes and either tumor grade 3 or tumor size ≥50 mm.

This action removes the prior requirement for Ki-67 testing (Ki-67 ≥20%) that had been part of the earlier approval for this population.

Supporting evidence

Efficacy was evaluated in monarchE, a randomized (1:1), open-label, two-cohort multicenter trial in adult women and men with HR-positive, HER2-negative, node-positive, resected early breast cancer. Patients received 2 years of abemaciclib plus standard endocrine therapy or endocrine therapy alone.

The major endpoint was invasive disease-free survival (IDFS). In the intent-to-treat population, the difference was statistically significant and primarily attributed to cohort 1. 48-month IDFS was 85.5% with abemaciclib plus endocrine therapy vs 78.6% with endocrine therapy alone.

Overall survival data were immature; in cohort 2, more deaths were observed with abemaciclib plus endocrine therapy vs endocrine therapy alone, so the indication was restricted to cohort 1.

Safety

Common adverse reactions (>20%) included diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.