Debu Tripathy, MD:Neratinib is also used in the setting of higher-risk disease. Like other therapies, we try to project, what is this patient’s risk of recurrence? And then, based on the hazard rate reduction that we project with that drug based on the clinical trials, we calculate what their absolute benefit would be. In this patient, I believe they have a high enough residual riskeven with all the therapy they’re receiving—such that the addition of neratinib may add a few more percentage points in lowering the risk of recurrence.
There are several different directions that are being taken to improve outcomes in HER2-positive breast cancer. Metastatic recurrences remain incurable, so our goal really needs to be to keep that number as low as possiblewith an acceptable risk profile, of course. The addition of other therapies that may complement these drugs is always going to be important. But then, we also have to realize that these drugs have side effects, there are costs, and there are convenience issues.
We don’t want to just keep piling on more and more drugs. We would like to be at a point where we can personalize therapy and know which patients do or do not need drugs. That falls into 2 general areas. One is understanding and discovering biomarkers that may predict who will respond to specific drugs. One example of a biomarker is PI3 kinase mutations, which seem to indicate some degree of resistance to trastuzumab and maybe to pertuzumab. They’re not really clinically used right now, but we need more biomarkers like that, and they need to be validated. Of course, we also need to look at other factors that predict who might be at higher risk of recurrence, whether it’s the stage or other clinical features, and this will help us be more precise.
The other movement that’s going on in this area is, are there patients in whom you can deescalate therapy? Someone who looks like they’re going to have an absolutely good outcome might not need the full year of antibody therapy. At this point, we don’t know that, but there are some discussions about identifying patientsnot with inflammatory cancers, but maybe who start off with node-negative cancers—who have a complete pathologic response and maybe don’t need to complete the full year of maintenance antibodies. Those kinds of studies are being discussed, as well.
Transcript edited for clarity.
60-year-old Woman WithHER2+ Inflammatory Breast Cancer