By David Bronstein

With its FDA approval, abemaciclib (Verzenio, Lilly) has risen to the top of the cyclin-dependent kinase (CDK) 4/6 inhibitor class of drugs for breast cancer, at least based on its unique indications, according to the agency.

“Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy,” said Richard Pazdur, MD, the director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Abemaciclib is approved for the treatment of hormone receptor (HR)-positive (HR+), HER2-negative advanced or metastatic breast cancer that has progressed after endocrine therapy. The drug is intended for use in combination with the endocrine therapy fulvestrant (Faslodex, AstraZeneca). 

Abemaciclib also is approved for monotherapy in patients who were previously treated with endocrine therapy and chemotherapy after cancer has metastasized, the FDA noted.

The CDK 4/6 inhibitor pathway that abemaciclib targets has been shown to play a major role in the growth of certain cancer cells. Two other CDK 4/6–inhibiting drugs are on the market: palbociclib (Ibrance, Pfizer) and ribociclib (Kisqali, Novartis).

Abemaciclib’s approval was based partly on results from the MONARCH 2 clinical trial of 669 patients with HR+, HER2-negative breast cancer who had progressed while receiving neoadjuvant or adjuvant endocrine therapy and who had not received chemotherapy since the cancer had metastasized. Patients were randomly assigned to receive abemaciclib (150 mg twice daily) plus fulvestrant (500 mg) or placebo plus fulvestrant. 

Median progression-free survival—the primary end point of the trial—was 16.4 months for patients in the abemaciclib-fulvestrant group versus 9.3 months for patients receiving fulvestrant monotherapy (hazard ratio, 0.553; 95% CI, 0.449-0.681; P<0.001), the investigators reported.

The most common adverse events (AEs) in the abemaciclib versus placebo arms were diarrhea (86.4% vs. 24.7%), neutropenia (46.0% vs. 4.0%), nausea (45.1% vs. 22.9%) and fatigue (39.9% vs. 26.9%), according to the MONARCH 2 investigators.

Data submitted for approval suggest that abemaciclib causes diarrhea at a higher rate than other CKD 4/6 medications, but causes less neutropenia, which some clinicians have cited as a factor to consider in choosing a drug in this class. 

Evidence for First-Line Therapy

Abemaciclib also may be affective as first-line treatment in postmenopausal women with HR+ HER2- advanced breast cancer, according to data from the MONARCH 3 study, which was presented at the European Society for Medical Oncology (ESMO) 2017 Congress in September.

In the phase 3 study, patients treated with abemaciclib plus an aromatase inhibitor (anastrozole or letrozole) in this setting had a 46% reduced risk for disease progression compared with controls. Objective response rates (ORR) also were superior in the abemaciclib combination group, at 48%, versus 34.5% for controls (P=0.002).

Commenting on the new findings, Giuseppe Curigliano, MD, director, Division of New Drug Development, European Institute of Oncology, University of Milan, Italy, said in a statement: “Abemaciclib is the third CDK4/6 inhibitor to be tested in advanced breast cancer and the MONARCH 3 trial confirms the role of this new class of agents in combination with endocrine therapy in the treatment of metastatic [disease].”

Dr. Curigliano added that “many patients with metastatic disease still receive chemotherapy, despite guidelines and data from clinical trials. This study confirms that we should avoid chemotherapy in hormone receptor positive, HER2 negative metastatic breast cancer if visceral crisis is not present.”

Pricing Announced

Lilly has announced pricing for abemaciclib, and it is in line with at least one of the other approved drugs in its class, according to a report in FiercePharma. A monthly course of the drug will cost $10,948, compared with a 28-day supply of ribociclib, priced at $10,950. However, Novartis has indicated that it offers flexible pricing for certain dosages, which may make its drug less expensive than the other agents in its class, the report noted.