Oncology Overview: Abemaciclib (Verzenio) for HR-Positive, HER2-Negative High Risk Early Breast Cancer

Abemaciclib (Verzenio; Lilly) is the first addition to adjuvant endocrine therapy approved by the FDA in two decades.

Worldwide, breast cancer (BC) has surpassed lung cancer as the most diagnosed form of the disease.1 In the United States, female BC makes up approximately 15% of all new cancer cases.1 Patients may notice a lump or change in breast size or shape.2

HR-Positive, HER2-Negative, Node-Positive Breast Cancer

Hormone receptor (HR)-positive BC indicates there are more estrogen and progesterone (hormones) receptors than normal.2 Human epidermal growth factor receptor type 2 (HER2)-negative is the term used to describe BC cells with a normal amount of HER2 on their surface.2 HER2-negative cancers do not respond to treatment with drugs targeting HER2.3 Node-positive indicates cancer has spread to lymph nodes.2

FDA Approval

The FDA initially approved abemaciclib (Verzenio; Eli Lilly and Company) in 2017 for certain types of HR-positive HER2-negative advanced or metastatic BC.4,5 The FDA recently approved abemaciclib in combination with endocrine therapy (ET) for the adjuvant treatment of patients with HR-positive HER2-negative, node-positive, early BC (EBC) at a high risk of recurrence and a Ki-67 score greater than or equal to 20%.4

Ki-67 is a protein that increases in cells just before division into new cells. An FDA-approved test measures the percentage of tumor cells positive for Ki-67.4,6 The FDA also expanded abemaciclib treatment for all indications when given in combination with ET to include men.4

The recent approval of abemaciclib was based on the phase 3 monarchE trial in men and women. Patients had HR-positive HER2-negative, node-positive, resected EBC with high risk of recurrence features.4

Randomized patients in the trial received 2 years of abemaciclib plus physician’s choice of standard ET (tamoxifen or an aromatase inhibitor) or standard ET alone. The study investigators found a statistically significant improvement in invasive disease-free survival for patients administered abemaciclib plus ET.4,5

Abemaciclib’s approval gives patients with high-risk HR-positive HER2-negative EBC hope of living cancer free. Patients want to do all they can to minimize the risk of cancer returning.4

Indications and Dose

Abemaciclib is an oral kinase inhibitor used to treat all stages of HER2-negative BC.5,7 Patients take abemaciclib as monotherapy or in combination with tamoxifen, an aromatase inhibitor, or fulvestrant.5

The recommended starting monotherapy dose is 200 mg orally twice daily, whereas the starting dose for combination therapy is 150 mg twice daily.5 Premenopausal and perimenopausal patients who take combination therapy (abemaciclib with fulvestrant or an aromatase inhibitor) require treatment with a gonadotropin-releasing hormone agonist to suppress ovarian function.5,7

Patients take abemaciclib at the same times every day and may take it with or without food.5 Health care providers should advise patients who vomit or miss a dose to take the next dose at the usual time.5

Prescribers should reduce dosing frequency to once daily for patients with severe hepatic impairment (Child Pugh-C).5 Patients with mild or moderate renal impairment do not require dosage adjustment. The pharmacokinetics are unknown in patients with severe renal impairment (CrCl < 30 mL/min).5

Mechanism of Action

Abemaciclib inhibits cyclin-dependent kinases 4 and 6 (CDK4 and CDK6).5 CDK4 and CDK6 are proteins in the body to help control cell division.7 Inhibition with abemaciclib interferes with kinases and stops cancer cells from dividing and growing.7

Adverse Effects (AEs)

The most common AEs are diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.5 Prescribers should consult the package insert for recommended abemaciclib dose modifications and management if an AE occurs (Table 1).5

Drug Interactions

Health care providers should instruct abemaciclib patients to avoid ketoconazole, a strong CYP3A inhibitor.5 Prescribers should consider dose reduction for other strong CYP3A inhibitors or for moderate CYP3A inhibitors.5

Providers should confirm patients avoid concomitant strong and moderate CYP3A inducers.5 Patients should not consume grapefruit products while taking abemaciclib.5

Fertility, Pregnancy, and Lactation

Lactating women should not breastfeed during treatment with abemaciclib and for at least 3 weeks following the last dose.5

Females of reproductive potential should use effective contraception during treatment and for 3 weeks following the last dose.5 Providers should inform males of reproductive potential that abemaciclib may impair fertility.5

About the Author

Ashley Walsh, PharmD, is a pharmacist at Mohegan Pharmacy in Uncasville, CT.

References

1. Cancer Stat facts: female breast cancer. National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Updated 2021. Accessed January 5, 2022. https://seer.cancer.gov/statfacts/html/breast.html

2. Breast cancer treatment (adult) (PDQ®)–patient version. National Cancer Institute. Updated October 4, 2021. Accessed January 6, 2022. https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#_125

3. Breast cancer HER2 status. American Cancer Society. Updated November 8, 2021. Accessed January 6, 2022. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html

4. FDA approves Verzenio (abemaciclib) as the first and only CDK4/6 inhibitor for certain people with HR+ HER2- high risk early breast cancer [News Release]. Eli Lilly and Company. October 13, 2021. Accessed January 5, 2022. https://investor.lilly.com/news-releases/news-release-details/fda-approves-verzenior-abemaciclib-first-and-only-cdk46

5. Verzenio. Prescribing Information. Eli Lilly and Company; 2021. Accessed January 5, 2022. https://pi.lilly.com/us/verzenio-uspi.pdf

6. Rate of cell growth. Breastcancer.org. Updated November 4, 2021. Accessed January 6, 2022. https://www.breastcancer.org/symptoms/diagnosis/rate_grade

7. Verzenio. Breastcancer.org. Updated October 14, 2021. Accessed January 5, 2022. https://www.breastcancer.org/treatment/targeted_therapies/verzenio