Managing Neutropenia Toxicity With CDK 4/6 Inhibitors Used to Treat Metastatic Breast Cancer

In a recent discussion on cyclin-dependent kinase (CDK) inhibitors with OncLive, Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discussed managing toxicities, like neutropenia, in patients with hormone receptor-positive metastatic breast cancer.

She explained that neutropenia is the most common toxicity for both palbociclib and ribociclib, but that serious neutropenia becomes less common further into the course of treatment.

“I think mainly because if a patient has had grade 4 neutropenia several times, they’re usually dose reduced,” Rugo said. “And so, then you stop seeing it, actually.”

However, while grade 3/4 neutropenia is seen commonly with both CDK4/6 inhibitors, which are approved as first-line therapy in combination with letrozole for patients with metastatic hormone receptor-positive breast cancer, there is not an increase in febrile neutropenia, which is important, because growth factors are not indicated for the type of neutropenia seen with CDK4/6 inhibitors.

“Clinicians, when they’re first starting to use the CDK4/6 inhibitors, often will believe that they should treat the neutropenia in a similar way to the way we treat chemotherapy-induced neutropenia where you give growth factors,” she explained.

In a separate discussion on CDK inhibitors to treat estrogen-receptor—positive metastatic breast cancer, Rugo explained that compared with abemaciclib, another CDK4/6 inhibitor, palbociclib and ribociclib cause more neutropenia. As a result, these 2 inhibitors are usually given for 21 days followed by 7 days off.

The same is not required for abemaciclib, which can be given on a continuous dosing schedule without a hold after 21 days, explained Sara Hurvitz, MD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center. However, while abemaciclib causes less neutropenia, there is more gastrointestinal toxicity.

“Abemaciclib has more potent activity against CDK4 and cyclin-D than CDK6, and this may be part of the reason why we’re seeing less neutropenia with abemaciclib and more GI toxicity,” Hurvitz said. “Palbociclib and ribociclib, in contrast to abemaciclib, have more grade 3/4 neutropenia but less GI toxicity.”