FDA Expands Early Breast Cancer Indication for Abemaciclib with Endocrine Therapy

On 3 March 2023, the US Food and Drug Administration (FDA) approved abemaciclib (Verzenio, Eli Lilly and Company) 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, lymph node-positive, early breast cancer at high risk of recurrence.

Patients defined as high risk included those having either ≥4 pathologic axillary lymph nodes (pALN) or 1-3 pALN and either tumour grade 3 or a tumour size ≥50 mm.

Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. Latest approval removes the Ki-67 testing requirement.

Full prescribing information for Verzenio is available here.

Efficacy was evaluated in monarchE (NCT03155997), a randomised (1:1), open-label, two-cohort multicentre study including adult women and men with HR-positive, HER2-negative, lymph node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of recurrence. To be enroled in cohort 1, patients must have either ≥4 pALN or 1-3 pALN and either tumour grade 3 or a tumour size ≥50 mm. To be enroled in cohort 2, patients could not be eligible for cohort 1 and must have had 1-3 pALN and tumour Ki-67 score ≥20%. Patients were randomised to either 2 years of abemaciclib plus physician’s choice of standard endocrine therapy (tamoxifen or an aromatase inhibitor) or standard endocrine therapy alone.

The major efficacy outcome measure was invasive disease-free survival (IDFS). A statistically significant difference was observed in the intent-to-treat population, primarily attributed to the patients in cohort 1 consisting of 5120 patients (91%); IDFS hazard ratio was 0.653 (95% confidence interval [CI] 0.567, 0.753). IDFS at 48 months was 85.5% (95% CI 83.8, 87.0) for 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 abemaciclib plus standard endocrine therapy compared to standard endocrine therapy alone (10/253 versus 5/264). Therefore, the indication was restricted to cohort 1.

The most common adverse reactions (≥20%) were diarrhoea, infections, neutropenia, fatigue, leukopenia, nausea, anaemia, and headache.

The recommended abemaciclib starting dose is 150 mg taken twice daily with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.

This review used the 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.

This application was granted priority review.