DR RUGO: It’s a fascinating study, because it was changed so much over time and shoved from one company to another as a drug that was never going to see the light of day. And in the end, they ended up with a trial where they had a short-term endpoint that was smaller than originally planned, where patients received neratinib for a year after they had completed their adjuvant trastuzumab, with the idea that potentially you could decrease late failures or even failures in the first few years.

As they were going along, they realized that the event rate would be very low. So they modified the trial partway through to increase the number of patients who had a higher risk of early recurrence, so patients with more positive nodes and those with residual disease after neoadjuvant chemotherapy. And then, of course, about 50% of patients have ER-positive or ER-negative disease, both with HER2 positivity. In this trial, there were more patients with ER-positive disease, relatively, because I think that those are the patients who have residual disease after neoadjuvant therapy. And those are the patients that seemed to get the benefit.

When I look at the overall trial benefit, it’s small, less than 3% in the overall population for disease-free survival. But if you look at the ER-positive group, it’s over 4%. And these are patients where we do see late recurrences. So I think that what we need from ExteNET are 2 things: One is ongoing follow-up of those patients to see if we’re really preventing recurrence in the long term and death from HER2-positive, ER-positive breast cancer. And if that’s the case, based on these impressive disease-free survival data, that would be great. I mean, that’s a way to really, I think, reduce risk in a patient population where we’ve had little progress other than adding in trastuzumab. Now, the ER-positive group.

And then the second thing is the control of toxicity. And I think that they are doing a really nice job in a study called the CONTROL trial, looking at a whole bunch of different sequential agents to control diarrhea. And I think that that’s going to be very important, because we’ll maintain quality of life during that second year. Certainly, I think all of us who have high-risk patients would love to have neratinib now in that patient population. We’ll wait and see what happens with the FDA review of the data, where they, of course, take a magnifying glass to the data that we can’t.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers