FDA Grants Dual Approval for T-DXd in HER2+ Early Breast Cancer

The Food and Drug Administration (FDA) has approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for two distinct indications in adult patients with HER2-positive early-stage breast cancer.

This decision expands the clinical utility of T-DXd into both the neoadjuvant and adjuvant settings, providing oncology nurses and the broader multidisciplinary team with new evidence-based options for high-risk patients.

Dual indications in early-stage disease

The first indication allows for T-DXd followed by a regimen of a taxane, trastuzumab, and pertuzumab (THP) as a neoadjuvant treatment for adults with Stage II or III HER2-positive (IHC 3+ or ISH+) breast cancer. The second indication is for the adjuvant treatment of adults with HER2-positive breast cancer who have residual invasive disease following neoadjuvant therapy involving trastuzumab and taxane-based treatments.

To support these indications, the FDA also approved two companion diagnostic devices: the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and the VENTANA HER2 Dual ISH DNA Probe Cocktail. These tests are essential for identifying patients who meet the HER2-positive criteria (IHC 3+ or ISH+) required for treatment.

Clinical efficacy: DESTINY-Breast11 and DESTINY-Breast05

The neoadjuvant approval was primarily supported by the DESTINY-Breast11 trial, a randomized, multicenter study involving 927 adults. Patients receiving four cycles of T-DXd followed by four cycles of THP achieved a pathological complete response (pCR) rate of 67.3%.

This was a statistically significant improvement compared to the 56.3% pCR rate observed in patients receiving dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP) (p=0.003).

For the adjuvant indication, the FDA reviewed data from the DESTINY-Breast05 trial, which compared T-DXd to trastuzumab emtansine (T-DM1) in 1,635 patients with residual invasive disease after neoadjuvant therapy. The results demonstrated a superior 3-year invasive disease-free survival (IDFS) rate of 92.4% for the T-DXd arm, compared to 83.7% for the T-DM1 arm (Hazard Ratio 0.47; p<0.0001). Additionally, the 3-year disease-free survival (DFS) rate was 92.3% for T-DXd versus 83.5% for T-DM1.

Nursing considerations and safety

Oncology nurses must be vigilant regarding the safety profile of T-DXd. The prescribing information includes a boxed warning for interstitial lung disease (ILD) and pneumonitis. Nurses should monitor patients closely for new or worsening pulmonary symptoms, such as cough, dyspnea, or fever. Additional warnings and precautions include neutropenia and left ventricular dysfunction.

In the adjuvant setting, the recommended dose is 5.4 mg/kg administered intravenously every three weeks for up to 14 cycles, or until disease recurrence or unacceptable toxicity. For neoadjuvant use, the same dosage is given for four cycles prior to starting the THP regimen.

Regulatory framework

The review was conducted under Project Orbis, an initiative by the FDA Oncology Center of Excellence that allows for concurrent submission and review among international regulatory partners, including Health Canada and the United Kingdom’s MHRA. While the adjuvant application received priority review and breakthrough designation, the neoadjuvant application was granted a standard review.

Reference

1. U.S. Food and Drug Administration. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage. Published May 15, 2026. Accessed May 16, 2026.