FDA
FDA expands Enhertu indications to include early HER2-positive breast cancer
HER2-targeted therapy has substantially improved outcomes in early-stage breast cancer, yet many patients still experience residual disease or recurrence despite standard treatment. FDA has now expanded the role of Enhertu (fam-trastuzumab deruxtecan-nxki) into earlier-stage HER2-positive disease, potentially changing treatment sequencing in both neoadjuvant and adjuvant settings.
On May 15, 2026, FDA approved two new indications for Enhertu in adults with HER2-positive (IHC 3+ or ISH+) early-stage breast cancer. The first approval covers neoadjuvant treatment with Enhertu followed by taxane, trastuzumab, and pertuzumab in stage II or III disease. The second approval covers adjuvant treatment for patients with residual invasive disease following neoadjuvant trastuzumab-based and taxane-based therapy.
The neoadjuvant approval was supported by the phase 3 DESTINY-Breast11 trial, which enrolled 927 adults with high-risk HER2-positive early-stage breast cancer. Pathologic complete response was achieved in 67.3% of patients receiving Enhertu followed by THP, compared with 56.3% receiving dose-dense doxorubicin/cyclophosphamide followed by THP (P=.003). At the time of analysis, event-free survival and overall survival data remained immature.
The adjuvant approval was based on the phase 3 DESTINY-Breast05 trial, which enrolled 1,635 patients with residual invasive disease after neoadjuvant therapy. At three years, invasive disease-free survival was 92.4% with Enhertu compared with 83.7% with trastuzumab emtansine (T-DM1), corresponding to a 53% relative reduction in invasive disease recurrence or death (hazard ratio 0.47; P<.0001).
The expanded indications may be clinically important because up to one in four patients with HER2-positive early breast cancer experience recurrence despite current standard therapies. Investigators noted that achieving pathologic complete response in the neoadjuvant setting is associated with improved long-term outcomes, while residual disease after surgery remains a major risk factor for recurrence.
FDA simultaneously approved companion diagnostic assays to identify eligible HER2-positive patients using immunohistochemistry or in situ hybridization testing.
The prescribing information includes a boxed warning for interstitial lung disease and pneumonitis. Clinicians should also monitor for neutropenia and left ventricular dysfunction. In DESTINY-Breast05, adjudicated drug-related interstitial lung disease/pneumonitis occurred in 9.6% of patients receiving Enhertu and included two grade 5 events.
“HER2-positive breast cancer is an aggressive disease, and our goal is to reduce the risk of recurrence for patients as early as possible to achieve the best long-term outcomes,” said Shanu Modi, MD, medical oncologist at Memorial Sloan Kettering Cancer Center. “These two new indications in HER2-positive early breast cancer will evolve how we treat patients in these settings and support trastuzumab deruxtecan as a potential new standard of care in early-stage disease.”
Sources:
AstraZeneca. (2026, May 15). Press release. Enhertu approved in the US for two new indications for patients with HER2-positive early breast cancer
U.S. Food and Drug Administration. (2026, May 15). Press release. FDA approves two separate indications for fam-trastuzumab deruxtecan-nxki in HER2-positive early-stage breast cancer