FDA Approves Enhertu After Positive DESTINY-Breast Phase III Results

AstraZeneca and Daiichi Sankyo announced that the US Food and Drug Administration (FDA) has approved Enhertu (trastuzumab deruxtecan) for both neoadjuvant and adjuvant treatment of HER2-positive early breast cancer, expanding the therapy’s use into earlier stages of disease. The approvals are supported by results from the Phase III DESTINY-Breast11 and DESTINY-Breast05 trials.

The neoadjuvant indication covers adult patients with HER2-positive Stage II or III breast cancer, where Enhertu is administered before surgery followed by taxane, trastuzumab, and pertuzumab (THP). The adjuvant indication applies to adult patients with HER2-positive breast cancer who have residual invasive disease following trastuzumab-based and taxane-based treatment.

In the DESTINY-Breast11 trial (NCT05113251), Enhertu followed by THP achieved a pathologic complete response (pCR) rate of 67.3% compared with 56.3% for dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP), representing an 11.2% improvement (95% confidence interval [CI]: 3.9-18.3; p=0.003). Event-free survival events occurred in 4.5% of patients, while overall survival events were reported in 1.9% at the time of analysis. The global study enrolled 927 patients and results were published in Annals of Oncology.

In the DESTINY-Breast05 trial (NCT04622319), Enhertu reduced the risk of invasive disease recurrence or death by 53% compared with trastuzumab emtansine (T-DM1) in patients with residual invasive disease after neoadjuvant therapy (hazard ratio [HR] 0.47; 95% CI: 0.34-0.66; p<0.0001). At three years, 92.4% of patients treated with Enhertu remained alive and free of invasive disease versus 83.7% in the T-DM1 arm. The study enrolled 1,635 patients globally, with findings published in The New England Journal of Medicine.

Shanu Modi, MD, Medical Oncologist at Memorial Sloan Kettering Cancer Center, said the approvals could help reduce recurrence risk earlier in treatment and potentially reshape standards of care in HER2-positive early breast cancer.

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, stated that the approvals address ongoing recurrence risks seen in up to one in four patients despite curative-intent treatment.

Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., said the approvals further expand Enhertu’s role across both early and metastatic HER2-positive breast cancer.

No new safety concerns were identified in either trial. In DESTINY-Breast05, drug-related interstitial lung disease (ILD)/pneumonitis occurred in 9.6% of patients receiving Enhertu compared with 1.6% in the T-DM1 arm, including two Grade 5 fatal events.

Enhertu is a HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. The therapy is already approved in more than 95 countries, including the US, for the treatment of HER2-positive metastatic breast cancer, with the latest FDA approvals further expanding its role into early-stage disease.

Reference

Enhertu approved in the US for two new indications for patients with HER2-positive early breast cancer

Study Details | NCT05113251 | Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer | ClinicalTrials.gov

Study Details | NCT04622319 | A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05) | ClinicalTrials.gov