Doctors receive guidance about side effects of a new treatment for breast cancer, a group of oral drugs that show promise for other cancers.
The latest treatment for breast cancer is a new group of oral drugs, the cyclin-dependent kinase (CDK) inhibitors. They show promise for the most common form of the disease, hormone receptor-positive (HR+) metastatic breast cancer — and, potentially, many other cancers. Doctors have been enthusiastic about having more breast cancer treatment options.
However, any new drug can cause unexpected problems as it reaches a larger population, especially patients taking other medications. Now, an independent comprehensive review of the side effects and drug interactions of three drugs gives them a green light and provides guidance to the many doctors forging ahead.
“CDK inhibitors have changed the landscape of management of HR+ breast cancer,” said Aditya Bardia, MD, a specialist in breast cancer at the Massachusetts General Hospital Cancer Center in Boston and the senior author of the review.
Cancer cells multiply fast. The new drugs block the activity of enzymes, particularly “CDK 4” and “CDK 6,” that help to regulate cell division — and, in that way, slow down the spread of the cancer. Doctors combine this treatment for breast cancer with hormone therapy, which fights the cancer by preventing hormones from binding with receptors on the cancer cells.
The reviewers looked at all existing public studies of three drugs, most of which had been submitted during the approval process at the U.S. Food and Drug Administration (FDA). The agency approved the first CDK inhibitor in February 2015, palbociclib (Ibrance). It approved ribociclib (Kisqali) in March this year, and a third, abemaciclib, is undergoing Phase 3 trials as a treatment for breast cancer. The agency designated all three drugs as “breakthrough therapies,” which means they were cleared for a streamlined approval process. Under those circumstances, guidance on interactions and side effects may be especially needed.
The review noted that the most common side effect of palbociclib and ribociclib is a decrease in white blood cells, a problem that can increase the chance of infection. The finding made sense, since the drugs block cell division, and proved able to reach blood cells in the bone marrow, including white blood cells. The problem shows up in about 40 percent of patients. But, the reviewers noted, white-blood counts usually returned to normal if the patient took a break from the drug or took a lower dose.
That issue wasn’t as common with abemaciclib, so it could be given continuously, but ademaciclib causes mild diarrhea in most patients.
Overall, the most common side effects, including nausea and hair loss, can be handled by medication breaks or lower doses.
Bardia and his team warned against combining the drugs with the antibiotic clarithromycin and grape juice, which block the activity of the enzyme, CYP3A, responsible for breaking down CDK 4 and CDK 6 in the liver. The combination could lead to a dangerous liver build up.
As doctors gain experience with CDK inhibitors as a treatment for breast cancer, other cancer specialists are watching with interest. Investigators are looking at the potential of the new class of drugs to fight lung, prostate, and ovarian cancer.
“The use of these drugs is likely to expand significantly in the near future,” commented Gabriel Hortobagyi at MD Anderson Cancer Center in Houston.
October 15, 2018
Christopher Nystuen, MD, MBA