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

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