AstraZeneca (AZ) and Daiichi Sankyo have announced Phase III DESTINY-Breast11 results showing Enhertu (trastuzumab deruxtecan) sequential with a THP (paclitaxel, trastuzumab and pertuzumab) regimen achieved 67.3% pathological complete response (pCR) versus 56.3% for ddAC-THP control in high-risk HER2-positive early breast cancer. The antibody-drug conjugate (ADC)-based combination demonstrated 11.2 percentage point improvement across HR-positive and -negative subgroups, with 81.3% residual cancer burden zero or one rate versus 69.1% in the control group. Safety profile showed lower grade three or higher adverse events incidence at 37.5% compared to 55.8% for the ddAC-THP regimen, with reduced left ventricular dysfunction and treatment discontinuation rates.

The trial represents the first successful incorporation of ADC in the neoadjuvant setting for HER2-positive breast cancer, with potential to replace anthracycline-based chemotherapy due to superior efficacy and cardiac safety. A supplemental biologics license application (sBLA) review is underway in the US, based on pCR endpoint with event-free survival data remaining immature at 4.5% maturity.

According to PharmCube's NextBiopharm® database, Enhertu holds seven approved indications globally, including HER2-positive breast cancer. Click here to request a free trial for NextBiopharm®.