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  6. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer
  1. Resources for Information | Approved Drugs

FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer

On May 15, 2026, the Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki (T-DXd, Enhertu, Daiichi Sankyo, Inc.) for two separate indications in adults with HER2-positive early-stage breast cancer. The first indication is for T-DXd followed by a taxane, trastuzumab, and pertuzumab (THP), for the neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test. The second indication is for T-DXd for the adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant treatment with trastuzumab (with or without pertuzumab) and taxane-based treatment.

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, both for identifying HER2-positive (IHC3+ or ISH+) patients for treatment with T-DXd, consistent with the approved drug labeling.

Full prescribing information for Enhertu will be posted on  Drugs@FDA . 

Efficacy and Safety

Efficacy of T-DXd followed by THP (T-DXd-THP) was evaluated in DESTINY-Breast11 (NCT05113251), a randomized, three-arm, open-label, multicenter trial that enrolled 927 adults with HER2-positive, high-risk, early-stage breast cancer. Patients were randomized (1:1:1) to receive eight cycles of neoadjuvant treatment with either, T-DXd for 4 cycles followed by THP (N=321) for 4 cycles, or doxorubicin and cyclophosphamide (ddAC) for 4 cycles followed by THP (ddAC-THP) (N=320), or an additional investigational therapy (N=286) for 8 cycles, until completion of planned therapy, or disease progression.

The major efficacy outcome measure was centrally assessed pathological complete response (pCR) rate, defined as the absence of invasive cancer in the breast and axillary lymph nodes following surgery. The pCR rate was 67.3% (95% CI: 61.9, 72.4) in the T-DXd-THP arm and 56.3% (95% CI: 50.6, 61.8) in the ddAC-THP arm (p-value 0.003), which was statistically significant. However, the secondary endpoints of event free survival (EFS) and overall survival (OS) were not statistically controlled or powered; the results from the adjuvant trial, DESTINY-Breast05, provided supportive evidence for the neoadjuvant indication.

Efficacy of T-DXd for adjuvant treatment was evaluated in DESTINY-Breast05 (NCT04622319), a randomized, two-arm, open-label, multicenter trial that enrolled 1635 adults with HER2-positive breast cancer with residual invasive disease after neoadjuvant therapy. Patients were randomized (1:1) to receive either T-DXd (N=818), or trastuzumab emtansine (T-DM1) (N=817), for a maximum of 14 cycles, or until disease recurrence or unacceptable toxicity.

The major efficacy outcome measure was invasive disease-free survival (IDFS), defined as the time from randomization to first occurrence of ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer or death from any cause. Additional efficacy outcome measures included disease-free survival (DFS) and overall survival (OS). The 3-year IDFS rate was 92.4% (95% CI: 89.7, 94.4) in the T-DXd arm and 83.7% (95% CI: 80.2, 86.7) in the T-DM1 arm (Hazard ratio 0.47 [95% CI: 0.34, 0.66]; p-value <0.0001). The 3-year DFS rate was 92.3% (95% CI: 89.5, 94.3) and 83.5% (95% CI: 79.9, 86.4) in the respective arms (Hazard ratio 0.47 [95% CI: 0.34, 0.66]; p-value <0.0001). At the time of the IDFS analysis, a total of 47 (2.9%) of patients had died across both study arms.

The prescribing information includes a boxed warning for interstitial lung disease (ILD) and pneumonitis, and warnings and precautions for neutropenia and left ventricular dysfunction.

Recommended Dosage

The recommended dose for neoadjuvant treatment is 5.4 mg/kg every three weeks for four cycles, followed by the THP regimen for four cycles. The recommended dose for adjuvant treatment is 5.4 mg/kg every three weeks for a maximum of 14 cycles unless there is disease recurrence or unacceptable toxicity.

These reviews were conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For these reviews, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), Switzerland’s Swissmedic (SMC), Singapore’s Health Sciences Authority (HSA), the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA), and the Israel Ministry of Health (ImoH). The applications may still be under review at the other regulatory agencies. 

These reviews used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. 

The application for the neoadjuvant indication was granted standard review and the application for the adjuvant indication was granted priority review. Fam-trastuzumab deruxtecan-nxki received breakthrough designation for the adjuvant indication. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov .

Follow the Oncology Center of Excellence on X: @FDAOncology.

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