FDA Grants Priority Review to Enhertu for HER2-Positive Breast Cancer

The U.S. Food and Drug Administration (FDA) has accepted a supplemental biologics license application (sBLA) and granted priority review for Enhertu (trastuzumab deruxtecan) to treat adult patients with HER2-positive breast cancer who have residual invasive disease after receiving neoadjuvant HER2-targeted treatment, AstraZeneca and Daiichi Sankyo have announced.

This regulatory milestone seeks to provide a new therapeutic option for patients whose cancer was not fully cleared by initial treatment before surgery. The FDA decision to grant Priority Review is reserved for medicines that could offer significant improvements in safety or efficacy over current options, with an action date anticipated during the third quarter of 2026.

Main data that support the findings

The application for this new indication is supported by results from the DESTINY-Breast05 phase 3 trial. Data from the study showed that Enhertu significantly reduced the risk of invasive disease recurrence or death by 53% when compared with Kadcyla (trastuzumab emtansine, T-DM1).

Further analysis of the trial data revealed the following benefits for patients:

• Invasive Disease-Free Survival (IDFS): Enhertu demonstrated a three-year IDFS rate of 92.4% compared with 83.7% for patients receiving Kadcyla. These findings remained consistent across all prespecified subgroups of patients.
• Disease-Free Survival (DFS): The medicine reduced the risk of disease recurrence or death by 53% versus Kadcyla.
• Distant Recurrence: Treatment with Enhertu lowered the risk of distant disease recurrence by 51% and the risk of brain metastases by 36% compared with Kadcyla.

Approximately one in five breast cancers are considered HER2-positive, a subtype often associated with aggressive disease and poor prognosis. While many patients receive neoadjuvant treatment before surgery, about half still have residual invasive disease in the breast or lymph nodes following that initial care. For these patients, the risk of the cancer returning or progressing to a metastatic state is significantly higher. In the United States, nearly 16,000 patients with HER2-positive early breast cancer receive treatment in the post-neoadjuvant setting after surgery each year.

Trial details

The DESTINY-Breast05 trial is a global, multicenter, randomized, open-label, phase 3 study evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus Kadcyla. The study enrolled 1,635 patients.

Participants in the trial were patients with HER2-positive early breast cancer who had residual invasive disease in the breast or axillary lymph nodes following neoadjuvant therapy. These patients were considered to be at a high risk of recurrence, defined as having inoperable cancer prior to neoadjuvant therapy or having pathologically positive axillary lymph nodes following surgery.

The primary endpoint of the trial was investigator-assessed IDFS, which tracks the time from randomization until the first instance of local, axillary or distant recurrence, or death from any cause. Secondary endpoints included overall survival, distant recurrence-free interval and brain metastasis-free interval. Enhertu is a HER2-directed antibody drug conjugate (ADC) consisting of a HER2 monoclonal antibody attached to topoisomerase I inhibitor payloads via cleavable linkers.

Safety

The safety profile of Enhertu observed during the DESTINY-Breast05 trial was consistent with the known profile of the medication. According to the reported data, no new safety concerns were identified in this specific patient population.

Enhertu is currently approved in more than 90 countries as a treatment for patients with HER2-positive metastatic breast cancer. This current sBLA, which also received breakthrough therapy designation, is being reviewed under Project Orbis to allow for concurrent submission among international partners. The move to bring this treatment to the post-neoadjuvant setting offers more patients the opportunity for sustained long-term outcomes and a potential path to cure.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

“Enhertu granted Priority Review in the US as post-neoadjuvant treatment for patients with HER2-positive early breast cancer,” news release; https://www.astrazeneca.com/media-centre/press-releases/2026/enhertu-granted-priority-review-in-the-us-as-post-neoadjuvant-treatment-for-patients-with-her2-positive-early-breast-cancer.html

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.