Dr Sara M. Tolaney Discusses the Role of Adjuvant Therapy in HER2-Positive Breast Cancer

Sara M. Tolaney, MD, MPH, instructor of medicine, Harvard Medical School, attending physician of medical oncology, Dana-Farber Cancer Institute, outlines the role of adjuvant therapy in treating patients with HER2-positive breast cancer, as well as the absence of biomarkers in this patient population.

Transcript

What role does adjuvant treatment play in the treatment of HER2-positive breast cancer?

I think the landscape in the adjuvant setting has also changed. Typically, the way we had previously approached patients with HER2-positive disease had been to either give a regimen called AC chemotherapy, followed by a taxane and Herceptin, or we would give a non-anthracycline-based therapy, which we call TCH, so using a docetaxel with carboplatin and trastuzumab. But, now we’ve seen introduction of a few new HER2 agents into the early-stage setting, one being pertuzumab.

So, there’s the APHINITY data that came out last year that showed that when you add pertuzumab to standard chemotherapy with trastuzumab, it resulted in an improvement in disease-free survival. That being said, that improvement was pretty small and seemed to be greater in patients who had higher risk disease. So, patients, for example, who had either node-positive disease or hormone-receptor-negative disease. So, at this point in time, we are, generally, incorporating pertuzumab into patients who have higher risk for HER2- positive disease.

One other agent we’re also including is neratinib, and this is a potent tyrosine kinase inhibitor against HER1, HER2, and HER4. This agent was studied in the exteNET trial, which looked at patients who had completed a year of trastuzumab based therapy, and then they got randomized to get a year of neratinib or nothing. They found that getting a year of neratinib, after completion of your year of trastuzumab, did provide additional benefit, but the benefit was really seen in the hormone-receptor-positive patients.

So, we do think about using neratinib in someone who had a particularly high-risk ER-positive tumor. I will said, that being said, the patients that were enrolled onto exteNET were all pertuzumab naïve, and now that we’re starting to integrate pertuzumab into adjuvant therapy, we really don’t have data about what the benefits are for using neratinib in someone who’s had prior pertuzumab.

Are there any identified biomarkers that guide a treatment approach for these patients?

Not at this time. I wish, but there aren’t any defined biomarkers that can help us predict which patients are likely to benefit from which treatment. I think where it would be particularly beneficial to us would be in trying to decide which patients are going to benefit from pertuzumab because the absolute benefit was small, then, I think there’s likely to be greater benefit in patients who may have certain biological predisposition to getting benefit from pertuzumab. So, there is ongoing work trying to look at biomarker predictors from the affinity trial that we’re waiting.