Potential of Trastuzumab Deruxtecan to Shift to First Line in HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH, discusses the efficacy of trastuzumab deruxtecan in the second-line setting as well as its potential to move into the first-line treatment in patients with HER2+ breast cancer.

On the second day of the Miami Breast Cancer Conference, we heard from 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, who took the “Zoom” stage to discuss the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the second-line setting. The issue focused on its potential to move into the first-line treatment of HER2+ breast cancer.

Trastuzumab deruxtecan is the standard-of-care in the second-line after adding significant progression-free survival benefit vs. T-DM1 in the DESTINY-Breast03 trial.

For patients with unresectable/metastatic HER2+ breast cancer who had received two or more prior anti-HER2-based therapies, Fam-trastuzumab deruxtecan-nxki was approved by the U.S. Food and Drug Administration in December 2019 for treatment in this patient population. This was based off of results from the previous phase II DESTINY-Breast01 trial.

The DESTINY-Breast03 trial is the “first, global phase III head-to-head trial of T-DXd against an active control in patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane.”

In the study, 524 previously treated patients were randomly assigned from North America, South America, Europe, Asia, and Oceania to receive T-DXd at 5.4 mg/kg or T-DM1 at 3.6 mg/kg every 3 weeks. Median progression-free survival was 25.1 months with T-DXd and 7.2 months with T-DM1

Based on results from the DESTINY-Breast03 trial, it becomes necessary to shift effective treatments earlier in treatment settings for patients with metastatic disease, especially if they result in a positive impact on long-term outcomes.

The examination of the potential of T-DXd as a first-line therapy has begun; the currently running randomized phase 3 DESTINY-Breast09 trial is looking at 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 the effectiveness T-DXd has demonstrated in later settings, it is possible that physicians could move the therapy up into earlier lines of treatment with the hope of potentially curing a greater number of patients with early-stage breast cancer.