Clinical Summary: 

• Design/Population: A post hoc analysis of the phase 3 DESTINY-Breast11 trial evaluated residual cancer burden outcomes in patients with high-risk HER2-positive early breast cancer receiving either neoadjuvant trastuzumab deruxtecan or dose-dense doxorubicin and cyclophosphamide followed by paclitaxel, trastuzumab, and pertuzumab.
• Key Outcomes: Trastuzumab deruxtecan plus paclitaxel, trastuzumab, and pertuzumab increased rates of minimal or no residual disease, with consistent benefit across subgroups and reduced overall residual tumor burden.
• Clinical Relevance: These results suggest the potential long-term benefit of trastuzumab deruxtecan plus paclitaxel, trastuzumab, and pertuzumab, even in patients with residual disease.

Results from a post hoc analysis of the phase 3 DESTINY-Breast11 trial demonstrated that neoadjuvant trastuzumab deruxtecan plus paclitaxel, trastuzumab, and pertuzumab improved residual cancer burden compared with dose-dense doxorubicin and cyclophosphamide plus paclitaxel, trastuzumab, and pertuzumab among patients with HER2-positive early breast cancer.

These results were presented by Lajos Pusztai, MD, DPhil, Yale Cancer Center, New Haven, Connecticut, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this study, 641 patients received either neoadjuvant trastuzumab deruxtecan (n = 321) or dose-dense doxorubicin and cyclophosphamide (n = 320) followed by paclitaxel, trastuzumab, and pertuzumab. Residual cancer burden was assessed via blinded central review based on surgical specimens and categorized into residual cancer burden classes (0–III), with residual cancer burden-0/I representing minimal or no residual disease.

At analysis, residual cancer burden-0/I rate was 81.3% in the trastuzumab deruxtecan arm and 69.1% in the doxorubicin and cyclophosphamide arm. Residual cancer burden-0/I rate was 78% in patients with HR-positive disease and 64.7% across all disease stages. Continuous residual cancer burden index distributions were also lower with trastuzumab deruxtecan compared with doxorubicin and cyclophosphamide (P = .0059). 

“Continuous [residual cancer burden] index distributions indicated lower residual burden with [trastuzumab deruxtecan plus paclitaxel, trastuzumab, and pertuzumab] than [dose-dense doxorubicin and cyclophosphamide plus paclitaxel, trastuzumab, and pertuzumab], indicating benefit among [patients] without [pathologic complete response].”

Source: 

Pusztai L. Residual cancer burden (RCB) following neoadjuvant treatment (NAT) with trastuzumab deruxtecan (T-DXd) followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (ddAC-THP) in high-risk HER2+ early-stage breast cancer (eBC). Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. LBA1.