Debu Tripathy, MD: This is a big question: Should we be using diarrhea prophylaxis? I think that if you use diarrhea prophylaxis, you are going to have less diarrhea. I have used that for quite some time with my patients, both with pertuzumab as well as with neratinib. However, we have also learned that if you take that approach, some patients will actually have constipation. Another approach that I sometimes use for my patients, depending on whether they’re naturally prone to constipation or diarrhea, is to not take it prophylactically but take it steadily to the first bowel movement, then take a double dose, and then take it every 6 hours. We do tell patients not to take more than 12 2-mg tablets a day. That way, they can stay on top of it. Sometimes we use drugs like Lomotil [atropine/diphenoxylate]. There is a nonrandomized study looking at diarrhea control called the CONTROL study that is testing a variety of other drugs, such as bile-sequestering agents like colestipol, and nonabsorbable steroids have also been tried. It looks like the bile-sequestering agents might be the most effective, at least with the preliminary data that have been presented so far. But we need a little more information and follow-up to solidify those recommendations.

Ruta D. Rao, MD: When starting neratinib, diarrhea prophylaxis should strongly be considered. Based on the CONTROL trial, we can say that loperamide with either budesonide or colestipol, or both, should be used. You can see that the results were significantly improved for the rates of diarrhea compared with the ExteNET trial, in which no prophylaxis was mandated.

Transcript Edited for Clarity