Neoadjuvant T-DXd then THP cuts residual cancer burden vs standard chemo in high-risk HER2-positive breast cancer

The DESTINY‑Breast11 trial compared three neoadjuvant approaches for patients with high‑risk HER2‑positive early‑stage breast cancer: T‑DxD followed by paclitaxel, trastuzumab and pertuzumab (THP), dose‑dense doxorubicin and cyclophosphamide followed by THP (ddAC‑THP), and T‑DxD alone. The T‑DxD‑THP arm was the focus of the final analysis after the monotherapy arm closed early per an independent data monitoring committee.

Among participants, 81.3% achieved a residual cancer burden of RCB‑0 or RCB‑I with T‑DxD‑THP, compared with 69.1% in the ddAC‑THP group. The proportion of patients with complete RCB (RCB‑0) was 68.8% versus 57.5% respectively, indicating a statistically significant shift toward lower residual disease (nominal P = .0059). Non‑pCR patients also showed a modest improvement in median RCB scores (1.5 vs 1.7).

The benefit was consistent across sub‑groups, including age, geographic region, hormone‑receptor status, disease stage and nodal involvement. Notably, hormone‑receptor‑positive patients reached 78.0% RCB‑0/RCB‑I versus 64.7% with ddAC‑THP, while hormone‑receptor‑negative patients achieved 90.4% versus 81.2%. Investigators reported a more favorable safety profile for the T‑DxD‑THP regimen compared with the standard chemotherapy sequence.

These findings suggest that incorporating T‑DxD into the neoadjuvant regimen may improve pathological outcomes for high‑risk HER2‑positive breast cancer, potentially influencing future treatment guidelines.