Drs Tripathy and McArthur touch on the use of extended adjuvant therapy with neratinib and identify patients who might be suitable for this regimen, including those high-risk patients with residual disease after neoadjuvant therapy.
Sara Hurvitz, MD: I know that there are studies ongoing looking at different therapies we can use in the adjuvant setting. Virginia brought up the use of neratinib. So I want to ask you, Debu, when are you using neratinib in the extended adjuvant setting in light of the fact that most of us are giving [our high-risk patients] drugs like pertuzumab and T-DM1 [trastuzumab emtansine]?
Debu Tripathy, MD: Well, I do think that there are patients at high risk for ongoing recurrence. I do use the ExteNET trial data, which took patients who had completed all of their therapy, including their trastuzumab, and randomized [them] to neratinib or not. And it did show a reduction in the odds of recurrence and particularly in hormone receptor-positive cancers and particularly in higher risk cases. Those were node-positive and especially in those with residual disease, which we know is a high-risk group, residual disease after neoadjuvant therapy. So that’s the group I use it in. That trial had a lot of issues in terms of how it was analyzed and conducted. It was a little unusual in that it passed hands several times, but it is the best we have, and I do think these patients are at high risk. So that’s the group I use it in.
Sara Hurvitz, MD: Heather, I’m going to push that a little bit further. You have a high risk, let’s say stage III node-positive, ER+, HER2 [human epidermal growth factor receptor 2]–positive. You give therapy, TCHP regimen [docetaxel, carboplatin, trastuzumab, and pertuzumab], [they have a] pathologic CR [complete response], but they started at stage III. Are you going to discuss neratinib with them?
Heather McArthur, MD: Well, as we know, pathologic complete response is very highly correlated for this subtype of breast cancer with cure rates. And so there’s an excellent forecast for that patient population. And there are a lot of issues, not just systemic therapy issues, but also surgery questions that are being asked and answered.
Do those patients really require axillary dissection if they’ve had clinical response? [There are] radiation questions. Do those patients require extensive radiation after surgery as well? So typically I would complete the year of HER2-directed therapy for that patient, but I probably wouldn’t prescribe neratinib. Neratinib is typically a drug that I prescribe, as Debu pointed out, in my very high-risk patients who have hormone receptor node-positive disease who don’t typically have a complete response. Of course, the ExteNET data predated our systemic use of pertuzumab so we don’t really know how to reconcile that data. But I have used it in selective patients who are particularly young and at very high risk of recurrence.
Transcript edited for clarity.