Updated survival results reinforced the superiority of trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) with clinically meaningful improvements in overall survival (OS), progression-free survival (PFS), and progression on next line of therapy or death (PFS2), among patients with HER2-positive metastatic breast cancer.

These updated data were first shared by Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, Tennessee, at the American Society of Clinical Oncology 2024 Annual Meeting.

The multicenter, open-label, phase 3 DESTINY-Breast03 trial enrolled 524 patients with HER2-positive metastatic breast cancer who had been treated with ≥1 prior anti-HER2 regimen. Patients were randomized on a 1-to-1 basis to receive either 5.4 mg/kg of trastuzumab deruxtecan (n = 261) or 3.6 mg/kg of trastuzumab emtansine (n = 263). The primary end point of this study was PFS by blinded independent central review and the key secondary end point was OS. Other secondary end points included PFS2 and safety.

With a median duration of follow-up of 43.0 months for trastuzumab deruxtecan and 35.4 months in trastuzumab emtansine, the median OS was 52.6 months and 42.7 months, respectively (hazard ratio [HR], 0.73). The 36-month OS rate was 67.6% in the trastuzumab deruxtecan arm and 55.7% in the trastuzumab emtansine arm. The median PFS was 29.0 months and 7.2 months, respectively (HR, 0.30). The 24-month PFS rate was 55.8% with trastuzumab deruxtecan and 20.6% with trastuzumab emtansine. The median PFS2 was 45.2 months with trastuzumab deruxtecan vs 23.1 month with trastuzumab emtansine.

The rates of treatment-emergent adverse events were consistent with those previously reported. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 16.7% of patients in the trastuzumab deruxtecan arm (4 new events since prior data cutoff) vs 3.4% in the trastuzumab emtansine arm (1 new event since prior data cutoff).

Dr Hamilton concluded, “This long-term follow-up further supports the previously demonstrated superiority of T-DXd over T-DM1 in patients with HER2-positive metastatic breast cancer whose disease progressed after trastuzumab and a taxane.” She went on, “These data continue to support the use of T-DXd as standard of care in patients with HER2-positive metastatic breast cancer who progressed after trastuzumab and a taxane, and show the longest OS observed in this setting.”

Source:

Hamilton E, Hurvitz S, Im SA, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03. Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #1025