Michel Velez, MD, medical oncologist at Holy Cross Hospital, discusses the management of neratinib (Nerlynx)-associated diarrhea in patients with early-stage HER2-positive breast cancer.

The incidence of grade 3 diarrhea was approximately 40% in the phase III ExteNET trial; however, diarrhea was managed reactively and not proactively, says Velez. In the phase II CONTROL trial, prophylactic intervention was used to reduce the rate of diarrhea that had been observed in the ExteNET trial.

Patients in the trial received neratinib and were randomized to 1 of 3 arms: loperamide only, the combination of budesonide and colestipol, or dose-escalated neratinib. Both the loperamide and combination arms showed a reduction in the incidence of grade 3 diarrhea. However, the combination resulted in a 50% reduction in the rate of grade 3 diarrhea, says Velez.

Among the 3 arms, the dose escalation arm appears to be the most promising. Dose-escalated therapy is not a new concept; it has shown much success when used in other cancer types, adds Velez. However, these data have yet to be reported from the third arm of the CONTROL trial. Ultimately, there are several options for managing diarrhea that can be used to get patients through the full course of neratinib therapy.

Michel Velez, MD

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Dr. Velez on Managing Neratinib-Associated Diarrhea in HER2+ Breast Cancer