- Mark Abramowicz, M.D., President: no disclosure or potential conflict of interest to report
- Jean-Marie Pflomm, Pharm.D., Editor in Chief: no disclosure or potential conflict of interest to report
- Brinda M. Shah, Pharm.D., Consulting Editor: no disclosure or potential conflict of interest to report
- Review the efficacy and safety of abemaciclib (Verzenio) for treatment of early breast cancer.
The oral cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib (Verzenio – Lilly), which was approved by the FDA in 2017 for treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, has now been approved for use in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%.1
HR-POSITIVE, HER2-NEGATIVE BREAST CANCER — About 70% of all breast cancers are HR-positive and HER2-negative. Standard treatment (a combination of surgery, radiation, and adjuvant/neoadjuvant chemotherapy plus adjuvant endocrine therapy) is effective for HR-positive, HER2-negative early breast cancer, but recurrence is common.2 Ki-67 is a prognostic biomarker for tumor proliferation; a score ≥20% is associated with early recurrence and poor prognosis.3,4
MECHANISM OF ACTION — CDKs 4 and 6 regulate the G1/S phase transition within the cell cycle; they are often overexpressed in HR-positive breast cancer, leading to cell cycle progression and cell proliferation. Inhibition of CDK 4/6 results in cell cycle arrest, senescence, and apoptosis.
CLINICAL STUDIES — FDA approval of abemaciclib for the new indication was based on the results of an open-label trial (monarchE) in 5637 women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer at high risk of recurrence (≥4 positive pathologic axillary lymph nodes or 1-3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67 score ≥20%). Patients were randomized to receive abemaciclib 150 mg twice daily for 2 years plus adjuvant endocrine therapy or endocrine therapy alone. Invasive disease-free survival (IDFS) at 2 years was 92.2% with combination therapy versus 88.7% with endocrine therapy alone, a statistically significant difference.5 IDFS at 3 years was 88.8% with combination therapy and 83.4% with endocrine therapy alone.6 Data beyond 3 years are not available.
Another CDK 4/6 Inhibitor – In a trial (Penelope-B) in 1250 women with HR-positive, HER2-negative early breast cancer at high risk of relapse, addition of the oral CDK 4/6 inhibitor palbociclib (Ibrance) 125 mg once daily for 13 cycles (21 days on, 7 days off) to adjuvant endocrine therapy did not improve IDFS compared to endocrine therapy alone.7
ADVERSE EFFECTS — The most common adverse effects (frequency ≥20%) of abemaciclib in the monarchE trial were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache. Severe (grade ≥3) adverse events occurred in 46% of patients in the abemaciclib group and in 13% of those in the placebo group. About 17% of patients in monarchE stopped taking abemaciclib because of adverse effects.
DOSAGE, ADMINISTRATION, AND COST — The recommended starting dosage of abemaciclib for the new indication is 150 mg twice daily taken in combination with tamoxifen or an aromatase inhibitor. The drug should be taken for a total of 2 years or until disease recurrence or unacceptable toxicity occurs. A 30-day supply of Verzenio costs about $13,870.8
CONCLUSION — Addition of the oral CDK 4/6 inhibitor abemaciclib (Verzenio) to adjuvant endocrine therapy improved invasive disease-free survival at 3 years in women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer at high risk of recurrence. No data are available on the durability of this effect beyond 3 years. Severe (grade ≥3) adverse events were reported in about 50% of patients.
- Abemaciclib (Verzenio) – a third CDK 4/6 inhibitor for breast cancer. Med Lett Drugs Ther 2017; 59:185.
- J Foldi et al. Defining risk of late recurrence in early-stage estrogen receptor-positive breast cancer: clinical versus molecular tools. J Clin Oncol 2019; 37:1365.
- A Fischer Maranta. Do you know the Ki-67 index of your breast cancer patients? Knowledge of your institution's Ki-67 index distribution and its robustness is essential for decisionmaking in early breast cancer. Breast 2020; 51:120.
- R Nishimura et al. Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Exp Ther Med 2010; 1:747.
- SRD Johnston et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol 2020; 38:3987.
- N Harbeck et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol 2021 September 29 (epub).
- S Loibl et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer – the Penelope-B trial. J Clin Oncol 2021; 39:1518.
- Approximate. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. November 5, 2021. Reprinted with permission by First Databank, Inc. All rights reserved. ©2021. www.fdbhealth.com/policies/drug-pricing-policy.