Dr Hilton on Trastuzumab Deruxtecan in HER2+ Metastatic Breast Cancer

Christie J. Hilton, DO, assistant professor, Department of Medicine, Drexel University College of Medicine, director, Academic Breast Oncology, Allegheny Health Network (AHN), AHN Cancer Institute, discusses the first-line standard of care (SOC) and changes in the second-line SOC, including key findings from the phase 3 DESTINY-Breast03 trial (NCT03529110), in patients with HER2-positive metastatic breast cancer.

In the first-line setting, patients with HER2-positive metastatic breast cancer should receive a taxane plus trastuzumab (Herceptin) and pertuzumab (Perjeta), a regimen that has remained standard, Hilton says. However, the most effective second-line treatment for patients with HER2-positive metastatic breast cancer has evolved from ado-trastuzumab emtansine (Kadcyla) to fam-trastuzumab deruxtecan-nxki (Enhertu), Hilton explains.

The randomized, open-label, multicenter DESTINY-Breast03 trial investigated the efficacy and safety of trastuzumab deruxtecan compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. At a median follow-up of 28.4 months in the trastuzumab deruxtecan arm and 26.5 months in the trastuzumab emtansine arm, the median progression-free survival (PFS) was 28.8 months in patients who received trastuzumab deruxtecan vs 6.8 months in those who received trastuzumab emtansine. In addition, the median overall survival (OS) was not reached (NR) with 72 OS events vs NR with 97 OS events in the trastuzumab deruxtecan and trastuzumab emtansine arms, respectively. The safety profile was similar between the 2 arms, with 56% and 52% of patients in the trastuzumab deruxtecan and trastuzumab emtansine arms, respectively, experiencing adverse effects of grade 3 or higher. Notably, interstitial lung disease occurred in 15% of patients who received trastuzumab deruxtecan vs 3% of those who received trastuzumab emtansine.

The PFS benefit with trastuzumab deruxtecan in this trial supports the use of this agent as the new second-line SOC in HER2-positive metastatic breast cancer, Hilton emphasizes. However, trastuzumab emtansine may still play a role in the treatment of patients with this disease, Hilton concludes.