US - FDA expands indication for Eli Lilly’s Verzenio (abemaciclib) for early breast cancer
The FDA approved Verzenio (abemaciclib) with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.
Patients defined as high risk included those having either ≥4 pALN (pathologic axillary lymph nodes) or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm.
Verzenio (abemaciclib) was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. Today’s approval removes the Ki-67 testing requirement. This application was granted priority review and reviewed with Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.
Clinical study(ies)
Efficacy was evaluated in monarchE (NCT03155997), a randomized (1:1), open-label, two-cohort multicenter Phase 3 trial including adult women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of recurrence. The study enrolled 5,637 adults.
To be enrolled in cohort 1, patients must have either ≥4 pALN or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm. To be enrolled in cohort 2, patients could not be eligible for cohort 1 and must have had 1-3 pALN and tumor Ki-67 score ≥20%. Patients were randomized to either 2 years of Verzenio (abemaciclib) plus physician’s choice of standard endocrine therapy (tamoxifen or an aromatase inhibitor) or standard endocrine therapy alone.
Results
The major efficacy outcome measure was invasive disease-free survival (IDFS). A statistically significant difference was observed in the intent-to-treat (ITT) population, primarily attributed to the patients in cohort 1 (cohort 1 N=5120 [91%]; IDFS HR 0.653 (95% CI: 0.567, 0.753)). IDFS at 48 months was 85.5% (95% CI: 83.8, 87.0) for Verzenio (abemaciclib) plus standard endocrine therapy and 78.6% (95% CI: 76.7, 80.4) for standard endocrine therapy alone.
Overall survival data remains immature. However, in cohort 2, more deaths were observed with Verzenio (abemaciclib) plus standard endocrine therapy compared to standard endocrine therapy alone (10/253 vs. 5/264). Therefore, the indication was restricted to cohort 1. Cohort 1 accounted for 91% of the study population.
The most common adverse reactions (≥20%) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.