Phase 3 trial of neoadjuvant T-DXd alone or followed by THP for high-risk HER2-positive early breast cancer

The multinational phase 3 DESTINY-Breast11 trial (147 centers in 18 countries) assessed efficacy and safety of neoadjuvant trastuzumab deruxtecan (T-DXd) alone or followed by paclitaxel + trastuzumab + pertuzumab (THP) versus dose-dense doxorubicine + cyclophosphamide (ddAC) followed by THP for high-risk HER2 positive early breast cancer (HER2+ EBC). The T-DXd alone arm enrolment closed early following Independent Data Monitoring Committee recommendation. The primary endpoint was pathological complete response. Neoadjuvant T-DXd-THP led to a statistically significant and clinically meaningful improvement in pCR rate versus ddAC-THP. Safety also favored T-DXd-THP, with lower rates of severe and serious adverse events and hematologic toxicities. The authors conclude that these data support T-DXd-THP as a more effective and less toxic neoadjuvant treatment than anthracycline-based therapy for HER2+ EBC.