C. Kent Osborne, MD
The treatment paradigm for HER2-positive breast cancer continues to focus on minimizing the role of chemotherapy and determining the optimal combination of HER2-targeted agents for specific patient subsets, says C. Kent Osborne, MD.
Osborne, director, Dan Duncan Comprehensive Cancer Center, Baylor College of Medicine, sheds light on the current and future treatment of HER2-positive breast cancer.
OncLive: Could you discuss overcoming resistance to HER2-targeted therapies?
There is a premise that HER2-amplified tumors are addicted to that oncogenic pathway. If you agree with that premise, then blocking that pathway completely ought to be really good therapy. Meaning, we might be able to get away with using only therapy that blocks HER2 and avoid chemotherapy, which, of course, is a lot more toxic.
So, now we have to validate that data, and if we do validate it then I think that [those two] biomarkers could be used in future trials to select patients that are most likely to respond to HER2-targeted therapy alone without chemotherapy. Basically, we are de-escalating treatment, because not everyone needs such aggressive treatment. De-escalation in the HER2 space requires knowledge of our biomarkers to select the right patients.
Have there been any recent impactful trials in this setting?
Trials of dual targeted therapy have shown that multiple agents are better than trastuzumab by itself, for the most part. When you block the entire receptor layer—all of the receptors that can trigger downstream signaling and growth of the tumor—it is much more effective than using trastuzumab alone. So, there are 8 or 9 of those trials now, some of them with chemotherapy and some without, that demonstrate the concept of dual targeted therapy that we reported in animal models years ago is correct.
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