FDA Approves Third Breast Cancer Indication for Verzenio

Used with an aromatase inhibitor, it substantially reduced tumor size and delayed disease progression

The FDA has approved abemaciclib (Verzenio, Eli Lilly and Co.) in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced or metastatic breast cancer.

This additional approval marks the third indication for abemaciclib within five months. In September 2017, abemaciclib became the first cyclin-dependent kinase (CDK) 4 and 6 inhibitor approved in combination and as a single agent in metastatic breast cancer. Specifically, abemaciclib was approved for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with HR+, HER2– advanced or metastatic breast cancer with disease progression following endocrine therapy, and as monotherapy for the treatment of adult patients with HR+, HER2– advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

The recommended dose of abemaciclib in combination with an AI is 150 mg orally twice daily, continued until disease progression or unacceptable toxicity. Abemaciclib is available in four tablet strengths—200 mg, 150 mg, 100 mg, and 50 mg.

This approval of abemaciclib as initial therapy in combination with an AI is based on the efficacy and safety demonstrated in the pivotal MONARCH 3 clinical trial. MONARCH 3 is a phase 3, randomized, double-blind, placebo-controlled trial evaluating abemaciclib in combination with an AI as initial endocrine-based therapy that enrolled 493 postmenopausal women with HR+, HER2– advanced breast cancer who had no prior systemic treatment for advanced disease. In patients who received neoadjuvant/adjuvant endocrine therapy, a disease-free interval of more than 12 months since completion of endocrine therapy was required.

This abemaciclib new drug application was given priority review as part of the FDA’s Expedited Programs for Serious Conditions. Abemaciclib was also granted breakthrough therapy designation in 2015 based on the phase 1 JPBA trial.

In MONARCH 3, abemaciclib dosed orally at 150 mg twice daily on a continuous schedule with an AI demonstrated a greater than 28-month median progression-free survival (PFS) in patients who received initial endocrine-based therapy for metastatic disease (28.2 months [95% confidence interval (CI), 23.5–NR] versus 14.8 months [95% CI, 11.2–19.2] with placebo plus an AI [hazard ratio (HR), 0.54; 95% CI, 0.418–0.698; P < 0.0001]).

In patients with measurable disease who received abemaciclib plus an AI (n = 267), an objective response rate (ORR) of 55.4% was achieved (ORR was defined as complete response plus partial response [CR + PR], and based upon confirmed responses; PR was defined as 30% or greater reduction in target lesions) (n = 148; 95% CI, 49.5–61.4), with 52.1% of patients having achieved a PR (n = 139) and 3.4% having achieved a CR (n = 9). In comparison, in the placebo-plus-AI group of patients with measurable disease (n = 132), ORR was 40.2% (n = 53; 95% CI, 31.8–48.5), with all women being partial responders. Median duration of response was 27.4 months with abemaciclib plus an AI (95% CI, 25.7–NR) versus 17.5 months with placebo plus an AI (95% CI, 11.2–22.2).

The most common adverse reactions in the MONARCH 1, 2, and 3 trials (all grades, at an incidence of 20% or greater) were diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia.

Source: Eli Lilly and Co.; February 26, 2018.