The U.S. Food and Drug Administration (FDA) has approved fam-trastuzumab deruxtecan-nxki (brand name Enhertu, also known as T-DXd) for two new uses in adults with HER2-positive early-stage breast cancer. These approvals expand treatment options both before and after surgery for patients whose cancer has not yet spread to distant parts of the body.
Before Surgery: Neoadjuvant Treatment
The first approval is for use before surgery (called neoadjuvant treatment) in adults with HER2-positive Stage II or III breast cancer. In this setting, T-DXd is given for four cycles, followed by a combination of taxane chemotherapy, trastuzumab, and pertuzumab for four additional cycles.
In a clinical trial of 927 patients with high-risk early-stage HER2-positive breast cancer, about 67% of those who received T-DXd before surgery had a pathological complete response—meaning no invasive cancer was found in the breast or lymph nodes after surgery. This compared to 56% of patients who received standard chemotherapy (doxorubicin and cyclophosphamide) followed by the same targeted therapy combination.
After Surgery: Adjuvant Treatment for Residual Disease
The second approval is for use after surgery (called adjuvant treatment) in patients who still have invasive cancer remaining after completing neoadjuvant HER2-targeted treatment. This addresses a high-risk situation where cancer cells were not completely eliminated by pre-surgery therapy.
In a study of 1,635 patients with residual disease after neoadjuvant therapy, those treated with T-DXd had significantly better outcomes than those who received trastuzumab emtansine (T-DM1), the previous standard treatment. At three years, about 92% of patients treated with T-DXd remained free of invasive disease recurrence, compared to about 84% of those treated with T-DM1.
Important Safety Information
Like many cancer treatments, T-DXd carries important risks. The prescribing information includes a boxed warning for interstitial lung disease (ILD) and pneumonitis, which are serious lung conditions that can occur during treatment. Other significant risks include low white blood cell counts (neutropenia), which can increase infection risk, and potential heart function problems (left ventricular dysfunction).
The FDA also approved two companion diagnostic tests to identify which patients have HER2-positive breast cancer and would be candidates for T-DXd treatment.
These approvals provide new options for patients with HER2-positive early-stage breast cancer at different points in their treatment journey, with the goal of reducing the risk of cancer returning after initial therapy.
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