Trastuzumab deruxtecan demonstrated durable anti-tumor activity in previously treated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, according to a study published in The New England Journal of Medicine and presented at the San Antonio Breast Cancer Symposium.
The two-part, open-label, single-group, multicenter, phase II DESTINY-Breast01 study included 184 patients with HER2+ metastatic breast cancer who had received a median of six prior lines of therapy, including trastuzumab, trastuzumab emtansine, pertuzumab, and other targeted therapies. Patients received trastuzumab deruxtecan 5.4 mg/kg of body weight (recommended dose from phase I study).
Response to treatment
In the intention-to-treat analysis, 112 patients (60.9%) responded to trastuzumab deruxtecan therapy (95% CI, 53.4-68.0), including 11 (6.0%) complete responses and 101 (54.9%) partial responses. After a median follow-up of 11.1 months (range, 0.7-19.9 months), median duration of response was 14.8 months (95% CI, 13.8-16.9), and median time to response was 1.6 months (95% CI, 1.4-2.6).
Median duration of progression-free survival was 16.4 months (95% CI, 12.7 to not reached).
Grade ≥3 treatment-related adverse events (AEs) occurred in 57.1% of patients and included decreased neutrophil count (20.7%), anemia (8.7%), and nausea (7.6%). AEs resulted in dose interruptions in 65 patients (35.3%) and dose reductions in 43 patients (23.4%). A total of 28 patients (15.2%) discontinued treatment due to an AE, most commonly related to pneumonitis or interstitial lung disease (ILD).
ILD occurred in 13.6% of patients (n=25), which the researchers said, “requires attention to pulmonary symptoms and careful monitoring.”