Lauren Carcas, MD, medical oncologist, Miami Cancer Institute, Baptist Health South Florida, discusses the design of the CONTROL trial and her personal experience with prophylaxis interventions for women with early-stage HER2-positive breast cancer receiving neratinib (Nerlynx).

The phase II CONTROL trial looked at how to control early-onset diarrhea within the first 2 cycles of treatment with neratinib. The trial examined standing doses of loperamide versus loperamide plus budesonide versus loperamide plus colestipol. There were 2 additional arms: colestipol with as needed loperamide and dose-escalated neratinib. Preliminary data show a significant improvement in the rate of grade 3 diarrhea across all groups, says Carcas.

Carcas, having participated in the trial, has had experience with standing doses of loperamide alone. None of these patients have had to come off of treatment, although they do experience more diarrhea than patients in the other arms. Budesonide with standing doses of loperamide is very well tolerated, although budesonide can cause issues with sugar and hypertension. Therefore, careful monitoring of patients who are receiving that intervention is required. Furthermore, although colestipol reduces the rate of diarrhea, it does cause constipation. Even so, no patients came off of treatment. However, dose reductions may be a necessary component over the course of administration, she adds.

Most recently, Carcas has explored dose-escalated neratinib and has found great success. Her patients are able to get up to full dose and do not require any delays in treatment or any dose reductions. Typically, patients are started on 160 mg with as-needed loperamide. If, after 14 days, patients are tolerating that dose without diarrhea, an additional tablet is added to get them up to 200 mg. If they are able to tolerate that dose over the course of the next week to 2 weeks, then patients receive the full dose of 240 mg.

Lauren Carcas, MD

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Dr. Carcas on the Design and Findings of CONTROL Trial in HER2+ Breast Cancer