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

Regulatory approval: On May 15, 2026, the FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for two indications in adults with HER2-positive (IHC 3+ or ISH+) early-stage breast cancer: (1) neoadjuvant T-DXd for 4 cycles followed by taxane/trastuzumab/pertuzumab (THP) for stage II–III disease, and (2) adjuvant T-DXd for patients with residual invasive disease after neoadjuvant trastuzumab (± pertuzumab) plus a taxane. Two HER2 companion diagnostics were also approved.

FDA approval (May 15, 2026): fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer

The FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for two separate indications in adults with HER2-positive (IHC 3+ or ISH+, by an FDA-authorized test) early-stage breast cancer:

  1. Neoadjuvant: T-DXd for 4 cycles followed by taxane + trastuzumab + pertuzumab (THP) for 4 cycles for stage II or III disease.

  2. Adjuvant: T-DXd for patients with residual invasive disease after neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment.

Key efficacy evidence

  • DESTINY-Breast11 (NCT05113251) (n=927; randomized, 3-arm, open-label): pCR was 67.3% (95% CI, 61.9–72.4) with T-DXd→THP vs 56.3% (95% CI, 50.6–61.8) with ddAC→THP (p=0.003). Secondary endpoints EFS and OS were not statistically controlled or powered; supportive evidence came from DESTINY-Breast05.
  • DESTINY-Breast05 (NCT04622319) (n=1635; randomized, 2-arm, open-label): 3-year IDFS was 92.4% with T-DXd vs 83.7% with T-DM1 (HR 0.47; 95% CI, 0.34–0.66; p<0.0001). At analysis, 47 deaths (2.9%) occurred across both arms.

Safety and dosing (label highlights)

Boxed warning for ILD/pneumonitis; warnings/precautions include neutropenia and left ventricular dysfunction. Recommended dose: 5.4 mg/kg q3w (neoadjuvant: 4 cycles; adjuvant: up to 14 cycles unless recurrence or unacceptable toxicity).

Companion diagnostics

FDA also approved PATHWAY anti-HER-2/neu (4B5) and VENTANA HER2 Dual ISH DNA Probe Cocktail to identify eligible patients.

Reviews were conducted under Project Orbis; applications may still be under review at other agencies.

Sources