Javier Cortés, MD, Ph.D., Founder, and director of the International Breast Cancer Center (IBCC), in Madrid, Spain. Dr. Javier Cortés Castán is a leading oncologist of international renown in the research and treatment of breast cancer. In this video, he speaks about Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.
Trastuzumab emtansine is the current standard of care for patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer whose illness has progressed after treatment with an anti-HER2 antibody plus a taxane.
In patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab and a taxane, we conducted a phase 3 multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody–drug conjugate) with those of trastuzumab emtansine. The primary outcome was progression-free survival (as judged by a blinded independent central review); secondary outcomes included overall survival, objective response, and safety.
At 12 months, the percentage of patients alive without disease progression was 75.8 percent (95 percent CI, 69.8 to 80.7) with trastuzumab deruxtecan and 34.1 percent (95 percent CI, 27.7 to 40.5) with trastuzumab emtansine (hazard ratio for progression or death from any cause, 0.28; 95 percent CI, 0.22 to 0.37; P0.001). The percentage of patients living at 12 months with trastuzumab deruxtecan was 94.1 percent (95 percent CI, 90.3 to 96.4) and 85.9 percent (95 percent CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95 percent CI, 0.36 to 0.86; prespecified significance boundary not reached). Overall response (complete or partial response) occurred in 79.7 percent (95 percent CI, 74.3 to 84.4) of trastuzumab deruxtecan patients and 34.2 percent (95 percent CI, 28.5 to 40.3) of trastuzumab emtansine patients. The incidence of drug-related adverse events of any grade was 98.1 percent with trastuzumab deruxtecan and 86.6 percent with trastuzumab emtansine, respectively, and 45.1 percent and 39.8 percent with trastuzumab emtansine. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5 percent of trastuzumab deruxtecan patients and 1.9 percent of trastuzumab emtansine patients; none of these events were grade 4 or 5.
Patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab plus a taxane had a decreased risk of disease progression or death when given trastuzumab deruxtecan than when given trastuzumab emtansine. Trastuzumab deruxtecan treatment was linked to interstitial lung disease and pneumonitis. (Daiichi Sankyo and AstraZeneca funded the DESTINY-Breast03 ClinicalTrials.gov number, NCT03529110. opens in new tab.)