Few serious toxicities from cyclin-dependent kinase 4/6 inhibitors in breast cancer

Last Updated: 2017-07-26

By Will Boggs MD

NEW YORK (Reuters Health) - Most serious toxicities related to cyclin-dependent kinase (CDK) 4/6 inhibitor treatment of breast cancer can be managed with careful monitoring and standard supportive care, according to a new review.

"While there is considerable excitement surrounding these drugs, these agents are different from endocrine therapies, and have a unique set of side effects and drug-drug interactions," Dr. Aditya Bardia from Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, told Reuters Health by email.

Palbociclib, ribociclib and abemaciclib are highly selective reversible inhibitors of CDK4 and CDK6 that have changed the treatment paradigm for metastatic hormone receptor-positive breast cancer.

Dr. Bardia and colleagues address the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer in their report.

Neutropenia is common with both palbociclib and ribociclib, but less so with abemaciclib, they write in The Oncologist, online July 13.

In any case, the incidence of febrile neutropenia is very low and the duration of grade 3 or 4 or worse neutropenia is around four days, so most hematologic abnormalities seen with these inhibitors can be adequately managed with standard supportive care.

Nausea and diarrhea can occur with palbociclib and ribociclib. Antiemetics can be used in patients receiving palbociclib, but caution should be used when coprescribing antiemetics with ribociclib due to the risk of QT prolongation.

Hematologic adverse events are less common with abemaciclib, whereas fatigue and gastrointestinal-related toxicity are more predominant.

Dose adjustments or dose holds are not generally required for grade 1 or 2 non-hematologic toxicities. But for grade 3 or higher toxicities that persist despite medical treatment, palbociclib and ribociclib should be withheld until symptoms resolve to a lower grade and should then be resumed at the next-lower dose.

Both palbociclib and ribociclib undergo hepatic metabolism, mostly mediated by CYP3A, so medications known to induce or inhibit this enzyme should be avoided if possible.

"CDK4/6 inhibitors are generally well-tolerated oral agents," the authors conclude. "Additional research is needed to better understand the toxicity profile and develop management strategies to minimize drug interruptions to optimize the highest possible therapeutic efficacy for patients with breast cancer."

"While the CDK4/6 inhibitors have not been compared head to head, the efficacy and toxicity profiles seem broadly similar," Dr. Bardia added. "Physicians should be aware of certain drug-drug interactions with CDK4/6 inhibitors, particularly common medications such as antibiotics, antihypertensives, and antiepileptics."

SOURCE: http://bit.ly/2uAN9ZW

Oncologist 2017.