FDA expands early breast cancer indication for abemaciclib with endocrine therapy
Regulatory approval: On March 3, 2023, the FDA approved abemaciclib (Verzenio) with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adults with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. The expanded indication removes the prior requirement for Ki-67 ≥20% testing and is restricted to patients meeting cohort 1 high-risk criteria from monarchE. Benefit was shown in invasive disease-free survival; overall survival remains immature.
FDA approval (March 3, 2023)
The FDA approved abemaciclib (Verzenio; Eli Lilly and Company) in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adult patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence.
High-risk definition: either ≥4 pathologic axillary lymph nodes (pALN), or 1–3 pALN with tumor grade 3 or tumor size ≥50 mm.
This approval removes the prior Ki-67 ≥20% testing requirement. The indication is restricted to cohort 1 from the monarchE trial.
Supporting evidence: monarchE (NCT03155997)
monarchE was a randomized (1:1), open-label, multicenter trial in adult women and men with resected HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. Patients received 2 years of abemaciclib plus standard endocrine therapy vs endocrine therapy alone.
Primary endpoint: invasive disease-free survival (IDFS). In the ITT population, the effect was primarily attributed to cohort 1 (N=5120; 91%): IDFS HR 0.653 (95% CI 0.567–0.753). 48-month IDFS was 85.5% with abemaciclib plus endocrine therapy vs 78.6% with endocrine therapy alone.
Overall survival data were described as immature; in cohort 2, more deaths occurred with abemaciclib (10/253) than control (5/264), supporting restriction to cohort 1.
Safety and dosing (label)
Common adverse reactions (≥20%): diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, headache. Recommended starting dose: 150 mg twice daily with tamoxifen or an aromatase inhibitor for 2 years, or until recurrence or unacceptable toxicity.