Trastuzumab Deruxtecan Outperforms Standard of Care in Previously Treated HER2–Positive, Metastatic Breast Cancer
Treatment with trastuzumab deruxtecan was associated with significantly lower risk of disease progression or death over the current standard treatment, trastuzumab emtansine, in patients with human epidermal growth factor receptor (HER2)–positive metastatic breast cancer, according to results from the DESTINY-Breast03 trial.
The phase 3, multicenter, open-label DESTINY-Breast03 trial aimed to compare the safety and efficacy of trastuzumab deruxtecan to those of trastuzumab emtansine in patients with HER2–positive, metastatic breast cancer previously treated with trastuzumab and a taxane. The trial randomized a total of 524 patients.
At 12 months, PFS was 75.8% for those treated with trastuzumab deruxtecan (95% confidence interval [CI], 69.8 to 80.7), compared with 34.1% (95% CI, 27.7 to 40.5) for those treated with trastuzumab emtansine (hazard ratio [HR] for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P <.001).
At 12 months, overall survival was 94.1% in the trastuzumab deruxtecan group (95% CI, 90.3 to 96.4), compared with 85.9% (95% CI, 80.9 to 89.7) in the trastuzumab emtansine group (HR for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached).
A complete or partial response occurred in 79.7% of the patients who received trastuzumab deruxtecan (95% CI, 74.3 to 84.4) but in only 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine.
However, adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group, but in only 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5.
The incidence of drug-related adverse events in general was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, while the incidence of drug-related adverse events of grade 3 or higher was 45.1% and 39.8%, respectively.
Source:
Cortés J, Kim S, Chung W, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi:10.1056/NEJMoa2115022.
