We must do better at trying to predict who those patients are going to be—who are going to develop CNS metastases and then target them in a preventative clinical trial. Otherwise, a lot of these combinations in the brain, such as neratinib and capecitabine, are also active systemically, so there may be a clinical trial that one could do.
The NALA trial is looking at this combination we used in our trial against lapatinib (Tykerb) and capecitabine in women without CNS disease. If it does show superiority, then that may be a potentially active systemic therapy that will hopefully prevent brain metastases. We don't know the answers to these questions, and they all need to be addressed in future studies.
What about dual-HER2 blockades?
Targeting dual anti-HER2 therapy is very appealing and may limit the side effects that you see, particularly if you use an agent like ONT-380, which doesn't have as much of a spillover effect and maybe less diarrhea than some of the other agents, such as lapatinib or neratinib. In our program, we are definitely looking at these combinations of dual HER2 therapy. In fact, ONT-380 is being looked at in combination with trastuzumab as dual HER2 combination therapy, and there are signs of activity. That is the future and maybe next steps.
What do you hope that community oncologists take from this study?
[They should just be] aware that there are a lot of clinical trials in this space right now for CNS disease, particularly in the HER2-positive space. For patients who are progressive after having some sort of standard local therapy, I would encourage local doctors to look around and see what clinical trials are available, because this is the perfect space to treat patients such as these. Reaching for the agents that are available to you makes sense, and of course, resist your local therapy options. I do hope that someday soon all our data will turn into approved regimens that will be available to all oncologists.
Freedman RA, Gelman RS, Melisko ME, et al. TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM). J Clin Oncol. 2017;35(suppl; abstr 1005).