Destiny-Breast04: Expanding T-DXd to HER2-Low

In this CHM Conversations clip, Dr. Paolo Tarantino distills how DESTINY-Breast04 redefined the therapeutic boundaries of trastuzumab deruxtecan (T-DXd), extending its reach from a shrinking HER2-positive population into the far broader domain of HER2-low metastatic breast cancer. Earlier studies like DESTINY-Breast01 and 03 changed outcomes in HER2+ disease, but with earlier cures reducing recurrence rates, the field had to ask: could T-DXd’s benefit transcend HER2-positivity?

DB04 provided a resounding yes. Building from an initial 40-patient cohort in Phase 1 showing ~40% response, the trial demonstrated that T-DXd nearly doubled progression-free survival and significantly improved overall survival versus chemotherapy in HER2-low patients—dismantling outdated binary HER2 classification and recasting minimal HER2 expression as a powerful therapeutic entry point.

🔬 Topics Covered:
• Reimagining HER2 as a gradient, not a binary
• DB04’s key findings and clinical implications
• Why T-DXd is reshaping metastatic breast cancer treatment