FDA Approves Enhertu for HER2-Positive Early-Stage Breast Cancer

The Food and Drug Administration approved Enhertu (fam-trastuzumab deruxtecan-nxki) on May 15, 2026, for two uses in adults with HER2-positive early-stage breast cancer, based on findings from the DESTINY-Breast11 and DESTINY-Breast05 trials. The approvals are intended to expand treatment options for patients receiving therapy before surgery and for those with residual invasive disease after neoadjuvant HER2-targeted treatment.

The first approval is for neoadjuvant treatment in adults with HER2-positive (IHC 3+ or ISH+) stage 2 or 3 breast cancer, followed by treatment with taxane, trastuzumab and pertuzumab (THP). The second approval is for adults with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment.

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, to identify eligible patients for treatment with Enhertu.

How Enhertu Improved Pathologic Complete Response in DESTINY-Breast11

The neoadjuvant approval was supported by results from the DESTINY-Breast11 trial, which evaluated Enhertu followed by THP compared with doxorubicin and cyclophosphamide followed by THP in patients with HER2-positive high-risk early-stage breast cancer.

The study’s main efficacy endpoint was pathological complete response (pCR), defined as the absence of invasive cancer in the breast and axillary lymph nodes after surgery.

Patients treated with Enhertu followed by THP achieved a pCR rate of 67.3% compared with 56.3% for patients treated with doxorubicin and cyclophosphamide followed by THP.

Although event-free survival and overall survival were evaluated as secondary endpoints, the trial was not statistically controlled or powered for those outcomes. The FDA noted that results from the DESTINY-Breast05 trial provided supportive evidence for the neoadjuvant indication.

DESTINY-Breast05 Showed Higher Invasive Disease-Free Survival

The adjuvant approval was supported by results from the DESTINY-Breast05 trial in patients with HER2-positive breast cancer who had residual invasive disease after neoadjuvant therapy.

The major efficacy endpoint was invasive disease-free survival (IDFS), which measured the time from randomization until invasive breast cancer recurrence or death from any cause.

The 3-year IDFS rate was 92.4% in the Enhertu arm compared with 83.7% in the trastuzumab emtansine (T-DM1) arm.

The 3-year disease-free survival rate was 92.3% for Enhertu and 83.5% for T-DM1.

At the time of the IDFS analysis, 47 patients (2.9%) had died across both study arms.

DESTINY-Breast11 Trial Design for Early-Stage HER2-Positive Breast Cancer

DESTINY-Breast11 was a randomized, three-arm, open-label, multicenter trial that enrolled 927 adults with HER2-positive, high-risk, early-stage breast cancer.

Patients were randomly assigned in a 1 to 1 to 1 ratio to receive one of three treatment approaches. One group received four cycles of Enhertu followed by four cycles of THP (321 patients). Another group received four cycles of doxorubicin and cyclophosphamide followed by four cycles of THP (320 patients). A third group received an additional investigational therapy for eight cycles (286 patients).

Treatment continued until completion of planned therapy or disease progression.

DESTINY-Breast05 Trial Evaluated Patients With Residual Disease

DESTINY-Breast05 was a randomized, two-arm, open-label, multicenter trial that enrolled 1,635 adults with HER2-positive breast cancer who had residual invasive disease after neoadjuvant therapy.

Patients were randomly assigned to receive either Enhertu (818 patients) or trastuzumab emtansine (817 patients) for up to 14 cycles or until disease recurrence or unacceptable side effects.

The recommended dose of Enhertu for neoadjuvant treatment is 5.4 mg/kg every three weeks for four cycles, followed by the THP regimen for four cycles.

For adjuvant treatment, the recommended dose is 5.4 mg/kg every three weeks for a maximum of 14 cycles unless disease recurrence or unacceptable side effects occur.

Safety

The prescribing information for Enhertu includes a boxed warning for interstitial lung disease and pneumonitis.

Additional warnings and precautions include neutropenia and left ventricular dysfunction.

References

1. “FDA Approves Fam-Trastuzumab Deruxtecan-Nxki for HER2-Positive Early-Stage Breast Cancer” News Release. U.S. Food and Drug Administration, May 15, 2026

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