This year, an estimated 246,660 women in the US will be diagnosed with breast cancer. The disease currently ranks as one of the most common causes of cancer deaths in American women. Fortunately, years of research into the biology of the disease have yielded some new and improved treatment options. And one recent class of drugs for breast cancer seems to be effective with limited major side effects in patients.
Breast cancer is generally classified into 3 subtypes according to the presence or absence of three receptors: estrogen, progesterone, and the epidermal growth factor receptor 2 (HER2). Typically, breast cancers positive for estrogen or HER2 respond well to hormone therapy. Researchers have also found that hormone receptor-positive (HR+) breast cancers respond well to a class of drugs known as cyclin-dependent kinase (CDK) inhibitors.
"CDK inhibitors have changed the landscape of management of HR+ breast cancer," said Aditya Bardia, a specialist in breast cancer at the Massachusetts General Hospital Cancer Center in Boston, and the senior study author. Just this year alone, the FDA approved two CDK inhibitors for breast cancer in quick succession: palbociclib (Ibrance) in February 2015, and ribociclib (Kisqali) in March 2017. A third drug in this class, abemaciclib, is currently tested in a Phase 3 trial.
CDK inhibitors block the kinases, namely CDK 4 and CDK 6. The result is a dramatic reduction of cell division, which is a hallmark trait of these cancer cells.
"Given the excitement with these drugs, there has been considerable uptake in clinical practice for management of patients with metastatic breast cancer," Bardia said. "However, these agents are different from endocrine therapies, and have a unique set of side effects. Therefore, we felt it was important to have a dedicated review article on clinical management of potential toxicities and drug interactions seen with the use of CDK 4/6 inhibitors and summarize practical management strategies for a medical oncologist."
In surveying the side effects of the three drugs, Bardia and his team found this class of drug had relatively minor side effects. Palbociclib and ribociclib, for example, had neutropenia (low white blood cells) as a common side effect, while abemaciclib was more commonly associated with diarrhea and fatigue.
"Ongoing trials are exploring the role of CDK 4/6 inhibitors in the adjuvant setting, so the use of these drugs is likely to expand significantly in the near future," said Gabriel Hortobágyi at MD Anderson Cancer Center in Houston, TX, a section editor of The Oncologist who was not involved in the review. "The article by Spring et al. summarizes the published toxicity data of the three leading CDK 4/6 inhibitors and provides clear, practical guidelines for managing the more common side effects and toxicities. Bringing together this information into one objective manuscript is a good service to the community."
Although CDK inhibitors can interact with other drugs, its safety and efficacy profile could expand the drug application to other cancer types, including lung, prostate, and ovarian cancer.
Additional source: Wiley via Science Daily