February 26, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the use of abemaciclib, a CDK4/6 inhibitor, in combination with an aromatase inhibitor (AI) as an initial endocrine therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. This is the third indication for abemaciclib, which is also approved in combination with fulvestrant or as monotherapy for women with HR-positive, HER2-negative advanced or metastatic breast cancer that progressed following initial endocrine therapy.
 
The approval was based on data from the phase III MONARCH 3 trial (NCT02246621) in which previously untreated patients with HER2-negative, HR-positive advanced breast cancer received abemaciclib in combination with a nonsteroidal AI, either anastrozole or letrozole.
 
A total of 493 patients were randomized to receive either abemaciclib at a dose of 150 mg, twice daily, or placebo with physician’s choice of AI. The estimated median progression-free survival was 28.2 months for patients receiving abemaciclib, but had not actually been reached. For patients receiving placebo, median PFS was 14.8 months. Overall, treatment with abemaciclib was associated with a 46% reduction in risk of disease progression or death
 
The most common treatment-related adverse event (AE) associated with abemaciclib was diarrhea, which occurred in 81.3% of patients receiving the CDK4/6 inhibitor and only 29.8% of patients receiving placebo. However, grade 3 diarrhea only occurred in 9.5% of patients. Neutropenia was also common and was seen in 41.3% of those treated with abemaciclib. Other AEs for patients receiving abemaciclib included fatigue, infections, nausea, abdominal pain, anemia, vomiting, alopecia, decreased appetite, and leukopenia.
 
The FDA recommends a starting dose of 150 mg, twice daily. Full prescribing information can be found here.
 
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Jonathan A. Bell
Published Online: Monday, February 26, 2018