Dr Tarantino on the Efficacy of Neoadjuvant T-DXd/THP in High-Risk HER2+ Breast Cancer

“For the first time, we saw that T-DXd has a role in the early-stage, curative [HER2-positive breast cancer] setting.”

Paolo Tarantino, MD, PhD, a research fellow in medicine at Dana-Farber Cancer Institute and Harvard Medical School, discussed the potential clinical implications of the phase 3 DESTINY-Breast11 trial (NCT05113251) investigating fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus a taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) in patients with high-risk, HER2-positive early breast cancer.

Tarantino noted that data presented at the 2025 ESMO Congress may lead to practice changes for several subtypes of breast cancer, including HER2-positive disease. He emphasized that for the first time, T-DXd demonstrated a definitive role in the early-stage, curative HER2-positive breast cancer setting.

In DESTINY-Breast11, neoadjuvant T-DXd/THP generated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate compared with dose-dense doxorubicin and cyclophosphamide plus THP (ddAC-THP). Patients in the T-DXd-THP arm (n = 321) achieved a pCR rate of 67.3%, which was superior to the 56.3% rate seen in the ddAC-THP arm (n = 320). The improvement in pCR for T-DXd/THP was observed across key subgroups, notably in both hormone receptor (HR)–positive and HR-negative disease.

For the HR-positive subgroup, the pCR rate was 61.4% with T-DXd/THP vs 52.3% with ddAC-THP. The HR-negative subgroup achieved a pCR rate of 83.1% for T-DXd/THP compared with 67.1% for ddAC-THP. Furthermore, treatment with T-DXd/THP resulted in a high proportion of patients (81.3%) having no or minimal residual invasive cancer following surgery compared with 69.1% of those receiving ddAC-THP.

Beyond efficacy, the safety profile of T-DXd-THP was favorable compared with ddAC-THP. T-DXd-THP led to reduced rates of grade 3 adverse effects (AEs; 37.5% vs 55.8%) and serious AEs (10.6% vs 20.2%). Tarantino specifically noted that the T-DXd-THP combination had less cardiotoxicity than ddAC-THP. Given these results—superior efficacy coupled with a favorable safety profile—Tarantino predicted that T-DXd/THP may be approved as a neoadjuvant treatment for patients with moderate- or high-risk disease.