Abemaciclib Receives FDA Approval for Hormone-Positive Breast Cancer Treatment

On 28 September 2017, the United States Food and Drug Administration FDA, for women whose disease continued progressing after hormone therapy, with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, approved abemaciclib(brand name Verzenio) with fulvestrant. It also approved abemaciclib alone for both women and men with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing after hormone therapy, who had received chemotherapy for metastatic disease and subsequently continued to progress.

Abemaciclib blocks cyclin-dependent kinase 4/6, part of intracellular growth signaling pathways in cancer. Palbociclib and ribociclibwere followed by abemaciclib, a third-generation cyclin-dependent kinase 4/6 inhibitor, in receiving FDA approval for breast cancer treatment.

Fulvestrant combination approval was based on a trial in women who had not previously received chemotherapy for metastatic disease, whose disease continued progressing after hormone therapy and who had hormone receptor-positive, HER2-negative metastatic breast cancer: the randomized, placebo-controlled, multicenter MONARCH 2 study.

In the study, 669 patients were divided into two groups receiving oral abemaciclib or placebo twice daily, plus intramuscular fulvestrant. In the first of the 28-day cycles, injections were given on days 1 and 15; from cycle 2 onward, on day 1, at 500 mg. Treatment continued until unmanageable toxicity or disease progression.

Median progression-free survival, the time disease remained controlled by treatment, was 16.4 months for fulvestrant plus abemaciclib and 9.3 months for placebo plus fulvestrant. Objective response rates were %48.1 with fulvestrant plus abemaciclib and %21.3 in the placebo plus fulvestrant arm.

Single-agent approval was based on women previously treated with taxane chemotherapy at any disease stage and one or two chemotherapy regimens for metastatic disease, whose disease continued progressing during or after endocrine therapy and who had measurable hormone receptor-positive, HER2-negative metastatic breast cancer, in the single-arm, open-label, multicenter MONARCH 1 study. It included 132 patients, who took oral abemaciclib 200 mg twice daily until progression or unmanageable toxicity. Objective response was %19.7, with median response duration of 8.6 months.

The most common side effects in patients receiving abemaciclib were diarrhea, reduced white blood cells (leukocytes), nausea, abdominal pain, infections, weakness, anemia, decreased appetite, vomiting, headache and reduced platelets. In patients receiving abemaciclib with fulvestrant, the most frequently reported (≥% 5) grade 3 or 4 side effects were reduced white blood cells, diarrhea, anemia and infections.

The recommended starting doseis 150 mg twice daily with fulvestrant or 200 mg twice daily as a single agent (monotherapy).