Dr. Tolaney on Potential of Trastuzumab Deruxtecan to Shift to First Line in HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, associate director, Susan F. Smith Center for Women's Cancers, senior physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, discusses the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the second-line setting and its potential to move into the first-line treatment of HER2-positive breast cancer.

It is critical to shift effective agents into earlier treatment settings for patients with metastatic disease, particularly if those therapies positively impact long-term outcomes, Tolaney says. T-DXd is the standard of care (SOC) in the second-line setting after data from the phase 3 DESTINEY-Breast03 trial (NCT03529110) demonstrated T-DXd elicited a median progression-free survival of 25.1 months, compared with 7.2 months for patients who received trastuzumab emtansine (T-DM1). This surpassed expectations set by previous trials, Tolaney explains.

Work has commenced to examine the potential of T-DXd as a first-line therapy, Tolaney notes. The ongoing randomized phase 3 DESTINY-Breast09 trial (NCT04784715) is examining 3 arms of patients receiving T-DXd plus pertuzumab (Perjeta), T-DXd plus placebo, or the SOC of taxane-based chemotherapy plus pertuzumab and trastuzumab (Herceptin).

Given how active T-DXd has proven to be in later settings, physicians could eventually move the agent into earlier lines of treatment to potentially cure more patients with early-stage disease, Tolaney concludes.