Dr. Tolaney on Deescalating Therapy in Stage I HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Women’s Cancers; director of Clinical Trials, Breast Oncology; and senior physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, discusses appropriately de-escalating treatment to reduce toxicities in stage I HER2-positive breast cancer.

One of the questions that arises with the use of HER2-targeted therapies is: Can therapy be appropriately de-escalated for patients who may be at lower clinical risk? Some pivotal trials focus on de-escalation strategies, specifically in patients with stage I HER2-positive disease. Previous data from the phase 2 APT trial suggest that patients with stage I HER2-positive cancers can have good outcomes with paclitaxel and trastuzumab (Herceptin). However, that is still a chemotherapy-based regimen that is associated with risks of neuropathy and alopecia. There has been interest in determining whether toxicities can be further reduced, adds Tolaney.

One trial that will be covered at the 19th Annual International Congress on the Future of Breast Cancer® East is the ATEMPT trial, which looked at administering 1 year of T-DM1 to patients with stage I HER2-positive disease. Patients were randomized to either T-DM1 or to the paclitaxel/trastuzumab regimen, as was administered in the APT trial. The ATEMPT trial did demonstrate that 1 year of T-DM1 was associated with a 3-year disease-free survival rate of 97.7%. The trial was then randomized to compare toxicities between the 2 arms. Higher rates of neutropenia, infusion reactions, alopecia, and neuropathy were seen with trastuzumab and paclitaxel, whereas with T-DM1, there were higher rates of thrombocytopenia and liver function abnormalities, concludes Tolaney.