September 28, 2017
On September 28, 2017, the Food and Drug Administration approved abemaciclib (VERZENIO™, Eli Lilly and Company) in combination with fulvestrant for women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. In addition, abemaciclib was approved as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
The approval in combination with fulvestrant was based on MONARCH 2, a randomized, placebo-controlled, multicenter trial in women with HR-positive, HER2-negative metastatic breast cancer with disease progression following endocrine therapy who had not received chemotherapy in the metastatic setting. The trial randomized 669 patients to receive either abemaciclib or placebo orally twice daily plus intramuscular injection of 500 mg fulvestrant on days 1 and 15 of cycle 1 and then on day 1 of cycle 2 and beyond (28-day cycles). Patients remained on continuous treatment with abemaciclib until development of progressive disease or unmanageable toxicity. Median progression-free survival for patients taking abemaciclib with fulvestrant was 16.4 months compared with 9.3 months for those taking placebo with fulvestrant (HR 0.553; 95% CI: 0.449, 0.681; p<0.0001). The objective response rate in patients with measurable disease taking abemaciclib with fulvestrant was 48.1% (95% CI: 42.6, 53.6) compared to 21.3% (95% CI 15.1, 27.6) in the placebo with fulvestrant treated patients.
The approval as monotherapy was based on MONARCH 1, a single-arm, open-label, multicenter study in women with measurable HR-positive, HER2-negative metastatic breast cancer whose disease progressed during or after endocrine therapy, had received a taxane in any setting, and who received one or two prior chemotherapy regimens in the metastatic setting. A total of 132 patients received 200 mg abemaciclib orally twice daily on a continuous schedule until progressive disease or unmanageable toxicity. Objective response rate was 19.7 percent (95% CI: 13.3, 27.5) with a median response duration of 8.6 months (95% CI: 5.8, 10.2).
The most common adverse reactions in greater than 20% of patients taking abemaciclib were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, and thrombocytopenia. The most frequently reported (≥5%) grade 3 or 4 adverse reactions in patients taking abemaciclib with fulvestrant were neutropenia, diarrhea, leukopenia, anemia, and infections.
The recommended starting doses are 150 mg twice daily in combination with fulvestrant or 200 mg twice daily as monotherapy.
Full dosing information is available at:
FDA granted priority review and Breakthrough Therapy Designation to abemaciclib for this indication. Approval was granted approximately three months prior to the due date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).