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.