High-Risk, Early-Stage Early HER2-Positive Breast Cancer: Trastuzumab Deruxtecan Combo Shows Promise

A new treatment strategy using trastuzumab deruxtecan (T-DXd, Enhertu) followed by a combination of trastuzumab (Herceptin), pertuzumab (Perjeta), and paclitaxel (THP) has shown significantly better results for patients with high-risk, early-stage HER2-positive breast cancer compared to the current standard therapy. This finding comes from the phase 3 DESTINY-Breast11 clinical trial.

Key Highlights:

Improved Pathologic Complete Response (pCR):
Patients who received T-DXd followed by THP before surgery had a higher rate of pathologic complete response (pCR)—meaning no signs of invasive cancer were found in the breast or lymph nodes at surgery—compared to those who received the standard dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP). Achieving pCR is linked to better long-term outcomes for patients.
Early Signs of Better Event-Free Survival (EFS):
While the data on event-free survival (EFS) are still being collected, early results suggest a positive trend for the T-DXd regimen, indicating it may help prevent cancer recurrence or progression better than the standard approach.
Safety Profile:
The safety of T-DXd followed by THP was similar to what is already known for these drugs, with no new safety concerns identified. Importantly, the rates of interstitial lung disease—a known risk with T-DXd—were similar between the new regimen and standard therapy.

What This Means for Patients:
These results suggest that T-DXd followed by THP could become a promising new option for patients with high-risk, early-stage HER2-positive breast cancer, potentially increasing the number of patients who are cancer-free after surgery and reducing the risk of the cancer returning.

Next Steps:
Full results from the DESTINY-Breast11 trial will be presented at an upcoming medical meeting and submitted to health authorities for review.

About Enhertu

Antibody drug conjugates (ADCs) are a type of targeted cancer medicine that deliver a cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. It is designed to deliver enhanced cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

Enhertu has a black box warning for interstitial lung disease and embryo-fetal toxicity. Enhertu is also FDA approved for appropriate patients with NSCLC, gastric or gastroesophagela junction cancer, and appropriate patients with HER2-positive solid tumors. Enhertu is FDA approved for the treatment of adult patients with unresectable or metastatic:

HER2-positive breast cancer who have received a prior anti-HER2-based regimen in the metastatic setting or in the neoadjuvant/adjuvant setting in appropriate patients after recurrence.
HR-positive HER2-low or HER2-ultralow breast cancer as determined by an FDA-approved test that has progressed on one or more endocrine therapies in the metastatic setting
HER2-low breast cancer as determined by an FDA-approved test who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of adjuvant chemotherapy.
Appropriate patients with HER2-positive gastric cancer, non-small cell lung cancer, and other solid tumors.

High-Risk, Early-Stage Early HER2-Positive Breast Cancer: Trastuzumab Deruxtecan Combo Shows Promise

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