FDA Approves Neoadjuvant and Adjuvant T-DXd for Patients With HER2-Positive Early Breast Cancer

Clinical Summary: 

• The FDA has approved neoadjuvant and adjuvant T-DXd based on the phase 3 DESTINY-Breast11 and DESTINY-Breast05 trials, where T-DXd demonstrated clinically meaningful benefit in both the neoadjuvant and adjuvant treatment settings for HER2-positive early breast cancer.
• These approvals expand the role of T-DXd into curative-intent HER2-positive breast cancer across both neoadjuvant and adjuvant treatment settings.

On May 15, 2026, the US Food and Drug Administration (FDA) approved neoadjuvant and adjuvant trastuzumab deruxtecan (T-DXd; Enhertu, Daiichi Sankyo) for patients with HER2-positive early breast cancer. This approval was based on results from the phase 3 DESTINY-Breast11 and DESTINY-Breast05 trials. 

In the DESTINY-Breast11 trial, 927 patients with HER2-positive, high-risk early breast cancer were randomized 1:1:1 to receive 4 cycles of either neoadjuvant T-DXd (n = 321) or dose-dense doxorubicin and cyclophosphamide (n = 320) plus a taxane, trastuzumab, and pertuzumab for 4 cycles, or 8 cycles of an additional investigational agent (n = 286) until completion of therapy or disease progression. The primary end point was centrally assessed pathological complete response (pCR), defined as the absence of invasive cancer in the breast and axillary lymph nodes following surgery. Key secondary end points were event-free survival (EFS) and overall survival (OS). 

At analysis, the pCR rate was 67.3% in the T-DXd arm and 56.3% in the dose-dense doxorubicin and cyclophosphamide arm (P = .003). EFS and OS were not formally powered for statistical testing in this analysis.

In the DESTINY-Breast05 trial, 1635 patients with HER2-positive breast cancer who had residual invasive disease following neoadjuvant treatment were randomized 1:1 to receive either T-DXd (n = 818) or trastuzumab emtansine (n = 817) for up to 14 cycles or until disease progression or unacceptable toxicity. The primary end point 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. Key secondary end points included disease-free survival (DFS) and overall survival (OS).

At analysis, the 3-year iDFS rate was 92.4% in the T-DXd arm and 83.7% in the trastuzumab emtansine arm (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.34 to 0.66; P <.0001). At the time of iDFS analysis, 2.9% of patients had died across both study arms. The 3-year DFS rate was 92.3% and 83.5%, respectively (HR, 0.47; 95% CI, 0.34 to 0.66; P <.0001). 

The recommended dose of neoadjuvant treatment is 5.4 mg/kg of T-DXd once every 3 weeks for 4 cycles followed by a taxane, trastuzumab, and pertuzumab for 4 cycles. The recommended dose of adjuvant treatment is 5.4 mg/kg of T-DXd once every 3 weeks for up to 14 cycles or until disease progression or unacceptable toxicity. 

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

The FDA also approved the PATHWAY anti-HER-2/neu Rabbit Monoclonal Primary Antibody assay and the VENTANA HER2 Dual ISH DNA Probe Cocktail as companion diagnostic devices to identify eligible patients with HER2-positive breast cancer for treatment with T-DXd.

Source: 

US Food and Drug Administration. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer. Accessed on May 18, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-two-separate-indications-fam-trastuzumab-deruxtecan-nxki-her2-positive-early-stage