Treatment for Breast Cancer Has Manageable Side Effects

Doctors receive guidance about side effects of a treatment for breast cancer, a group of oral drugs that show promise for other cancers. Here’s what you should know.

The latest treatment for breast cancer is a group of three oral drugs, 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.

Any new drug can cause unexpected problems as it reaches a larger population, especially patients taking other medications. But experience with the drugs treatments has been largely positive.

The drugs include palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio).

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In a review of eight clinical trials, for example, researchers from a cancer center at the University of Toronto concluded that they were similarly effective and tolerated (patients were most likely to drop one, abemaciclib, because of diarrhea).

A separate group, from the University of Munich, had the same conclusion, noting that side effects are manageable and that the drugs slowed deterioration in a patient’s qualify of life and helped control pain.  

An earlier comprehensive review of the side effects and drug interactions of the drugs gave them a green light and provided guidance to 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. CDK drugs block the activity of enzymes, particularly “CDK 4” and “CDK 6,” that help to regulate cell division, slowing the spread of cancer. Doctors combine the treatment 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 were submitted during the approval process at the U.S. Food and Drug Administration (FDA).

The FDA has since approved all three CDK inhibitors. 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 are 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 it does cause mild diarrhea in many patients. Overall, medication taking breaks or lower doses can minimize the most common side effects, including nausea and hair loss.

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 cancers.

“The use of these drugs is likely to expand significantly in the near future,” said Gabriel Hortobagyi, MD, at MD Anderson Cancer Center in Houston.

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