Abemaciclib Receives FDA Approval for Certain Metastatic Breast Cancers

Clinicians now a have tool for treating women who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after initial therapy failed. On September 28, 2017, the U.S. Food and Drug Administration (FDA) approved abemaciclib (Verzenio) for this patient population. Abemaciclib is approved to be given in combination with an endocrine therapy (fulvestrant) after a woman suffers relapse on endocrine therapy. It is also approved to be given alone, if patients were previously treated with endocrine therapy and chemotherapy after metastasis.

"[Abemaciclib] 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, in a press release. Pazdur is 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 provides a new alternative for a large number of patients. It is estimated that approximately 72% of patients with breast cancer have tumors that are HR-positive and HER2-negative. This agent blocks cyclin-dependent kinases (CDKs) 4 and 6, which are involved in promoting cancer cell growth. There are two other drugs in this class that are approved for treating breast cancer. Palbociclib was approved in February 2015 and ribociclib was approved in March 2017.

The safety and efficacy of abemaciclib in combination with fulvestrant were studied in a randomized trial of 669 patients with HR-positive, HER2-negative breast cancer. All patients had progressed after treatment with endocrine therapy and had not received chemotherapy once the cancer had metastasized. The study showed that the median progression-free survival (PFS) for patients on abemaciclib with fulvestrant was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant.

The safety and efficacy of this agent as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer. All patients had progressed after treatment with endocrine therapy and chemotherapy after their disease had metastasized. The study showed 19.7% of patients taking abemaciclib experienced complete or partial shrinkage of their tumors for a median of 8.6 months.

The most common side effects associated with abemaciclib include diarrhea, neutropenia leukopenia, nausea, abdominal pain, infections, fatigue, anemia, decreased appetite, vomiting, and headache. Serious side effects include diarrhea, neutropenia, elevated blood liver enzymes, and deep venous thrombosis/pulmonary embolism.

Abemaciclib is being investigated in clinical trials in patients with breast cancer, non-small cell lung cancer, and pancreatic cancer, according to drug developer Eli Lilly. The company said many human tumors acquire alterations, which can include mutations that directly activate CDK4 and CDK6.