Dr. Tolaney on the APT and ATEMPT Trials 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 the phase 2 APT and APTEMPT trials in stage I HER2-positive breast cancer.

One question that comes up is how to appropriately de-escalate therapy for patients who may be at a lower clinical risk, says Tolaney. Some important trials to look at include those with de-escalation strategies, specifically for patients with stage I HER2-positive disease. Data from the phase 2 APT trial, for example, suggest that patients with stage I HER2-positive cancers can do very well with paclitaxel (Taxol) and trastuzumab (TH; Herceptin) alone. However, this is still is a chemotherapy-based regimen and is associated with risks of neuropathy and hair loss. This has led to further interest to see if the field can do better by reducing toxicities, says Tolaney.

One trial that aims to do this is the phase 2 ATEMPT trial, which looked at administering a year of ado-trastuzumab emtansine (T-DM1; Kadcyla) to patients with stage I HER2-positive disease. Patients were randomized to a year of T-DM1 or TH, as was administered in the APT trial. That study did demonstrate that a year of T-DM1 was associated with very good long-term outcomes; this can be seen in the 3-year DFS of 98.7%.

The trial was then randomized to compare toxicities between the 2 arms, though investigators found that there weren't any clinically relevant differences; the absolute percentages were almost identical, explains Tolaney. However, the toxicity profiles were very different. There were higher rates of neutropenia, infusion reactions, alopecia, and neuropathy with TH, whereas with T-DM1 there were higher rates of thrombocytopenia and liver function abnormalities, concludes Tolaney.