Virginia Kaklamani, MD, DSc, presents results of the DESTINY-Breast03 clinical trial of trastuzumab deruxtecan compared with trastuzumab emtansine as treatment for patients with HER2-positive metastatic breast cancer.
Virginia Kaklamani, MD, DSc, discusses data from the following presentation:
Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: results of the randomized, phase 3 study DESTINY-Breast03. (Cortes, ESMO 2021, Abstract LBA1)
T-DXd is a HER2-targeting antibody-drug conjugate approved for patients with advanced HER2 (human epidermal growth factor receptor 2)–positive metastatic breast cancer (mBC) based on the results from DESTINY-Breast01 (NCT03248492). This is the first report of DESTINY-Breast03 (NCT03529110), a multicenter, open-label, randomized phase 3 study comparing the efficacy and safety of T-DXd vs T-DM1 in patients with HER2+ mBC previously treated with trastuzumab and taxane. This is the first reported randomized study of T-DXd in breast cancer.
Patients were randomized 1:1.
The primary end point was progression-free survival (PFS) by blinded independent central review (BICR).
Secondary end points include overall survival (OS), objective response rate (ORR), duration of response, PFS by investigator, and safety.
As of May 21, 2021, 524 patients were randomized. Median age was 54 years (range, 20-83).
Median treatment duration was 14.3 months (range, 0.7-29.8) with T-DXd vs 6.9 months (range, 0.7-25.1) with T-DM1.
The hazard ratio (HR) for PFS was 0.2840 (P = 7.8 x 10-22); median PFS not reached for T-DXd vs 6.8 months for T-DM1.
The estimated 12-month OS event rates were 94.1% (95% CI, 90.3-96.4) for T-DXd and 85.9% (95% CI, 80.9-89.7) for T-DM1; HR: 0.5546 (95% CI, 0.3587-0.8576; P = .007172 did not cross prespecified boundary for significance).
Similar rates of treatment-emergent adverse events were observed. No drug-related deaths occurred in either arm. Adjudicated drug-related interstitial lung disease (ILD) occurred in 10.5% of patients with T-DXd (most [9.7%] grade 1/2; 0 grade 4/5) vs 1.9% with T-DM1 (all grade 1/2).
T-DXd demonstrated a highly statistically significant and clinically meaningful improvement in PFS vs T-DM1 in patients previously treated with trastuzumab and taxane for HER2+ mBC. These data confirm that T-DXd (trastuzumab deruxtecan) is tolerable with manageable toxicity and a significant improvement in ILD profile vs studies performed in more heavily pretreated patients. This study will lead to a paradigm shift in the treatment of HER2+ mBC.