Dr Tolaney on Potential Changes to Early-Stage HER2+ Breast Cancer Management

“We are making dramatic strides in improving outcomes for our [patients with] HER2-positive [disease], as you can see across all disease settings.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women's Cancers and a senior physician at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, discussed the rapid evolution of treatment protocols for early-stage HER2-positive breast cancer following the emergence of recent clinical trial data.

Notably, this topic stemmed from recent findings in both neoadjuvant and adjuvant settings, where Tolaney has observed a significant clinical shift toward the use of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu). She noted that results from the phase 3 DESTINY-Breast11 trial (NCT05113251), which investigated sequential T-DXd followed by a taxane plus trastuzumab (Herceptin) and pertuzumab (Perjeta), yielded a pathologic complete response (pCR) rate of 67.3%. These data represent the highest pCR rate recorded to date in HER2-positive disease, including a 61.4% pCR rate in the hormone receptor–positive, HER2-positive patient population, a group that historically sees significantly lower response levels.

Tolaney further emphasized the success of T-DXd in the high-risk residual disease setting as seen in the phase 3 DESTINY-Breast05 trial (NCT04622319). She pointed out that in this trial, T-DXd reduced the risk of recurrence when compared with the previous SOC, ado-trastuzumab emtansine (Kadcyla). Despite these strides, Tolaney observed that the methods for tailoring these potent therapies to individual patients remain a complex challenge for clinical teams. She noted that although outcomes are improving across all disease settings, there is an ongoing need to determine the precise amount of treatment each patient requires and the optimal timing for its administration. To bridge this gap in clinical application, Tolaney advocated for the development of further clinical trials to help breast medical oncologists define these treatment individualization strategies.