European Union approves Enhertu combined with pertuzumab as the first new first line treatment regimen in over ten years for HER2 positive metastatic breast cancer

Approval based on the Phase III DESTINY-Breast09 trial, which showed that AstraZeneca and Daiichi Sankyo’s Enhertu plus pertuzumab cut the risk of disease progression or death by 44 percent compared with THP, with median progression free survival surpassing three years

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan), combined with pertuzumab, has received approval in the European Union for first line treatment of adult patients with unresectable or metastatic HER2 positive breast cancer.

The European Commission’s approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use and is based on results from the Phase III DESTINY-Breast09 trial, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting and later published in The New England Journal of Medicine.

Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital and the Vall d’Hebron Institute of Oncology in Barcelona, a steering committee member and investigator for the DESTINY-Breast09 trial, said that for patients diagnosed with HER2 positive metastatic breast cancer, maintaining disease control for as long as possible in the first line setting remains a critical treatment goal. She said the combination of trastuzumab deruxtecan and pertuzumab marks a significant therapeutic advance, with progression free survival exceeding three years compared with roughly two years under the current standard of care, and noted it has the potential to become the new first line standard of care.

Dave Fredrickson, executive vice president of the oncology haematology business unit at AstraZeneca, said the approval brings Enhertu to patients in the EU earlier in the course of their metastatic disease and sets a new benchmark for progression free survival in the first line setting. He said HER2 positive metastatic breast cancer is an aggressive disease, so giving patients the best chance at improved long term outcomes depends on starting effective HER2 directed therapy early and continuing treatment for as long as patients continue to benefit.

Ken Keller, global head of oncology business and president and CEO of Daiichi Sankyo, Inc., said this milestone represents the second new indication for Enhertu in the EU within just two months, following the recent tumour agnostic approval, underscoring the company’s goal of bringing the medicine to more eligible patients as quickly as possible. He said the approval of Enhertu combined with pertuzumab has the potential to reshape clinical practice in the first line treatment setting for patients with HER2 positive metastatic breast cancer.

In the DESTINY-Breast09 trial, Enhertu combined with pertuzumab reduced the risk of disease progression or death by 44 percent compared with a regimen of taxane, trastuzumab, and pertuzumab (based on a hazard ratio of 0.56; 95% confidence interval 0.44 to 0.71; p<0.00001) in patients with HER2 positive metastatic breast cancer who had not previously received chemotherapy or HER2 targeted therapy, or who had received neoadjuvant or adjuvant HER2 targeted therapy more than six months before their diagnosis of advanced or metastatic disease. Median progression free survival was 40.7 months with Enhertu plus pertuzumab, compared with 26.9 months for the THP regimen, as assessed by blinded independent central review.

The safety profile of Enhertu combined with pertuzumab was consistent with the known profiles of each treatment individually, and no new safety concerns emerged.

Based on the DESTINY-Breast09 results, Enhertu combined with pertuzumab has been included in the ESMO Clinical Practice Guidelines as a Category IA first line treatment option for patients with metastatic HER2 positive breast cancer, regardless of hormone receptor status.

Enhertu is also currently under review in the EU for patients with HER2 positive breast cancer who have residual invasive disease following neoadjuvant HER2 targeted treatment, based on data from the DESTINY-Breast05 trial.

Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

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Related Topics and Keywords

breast cancer, enhertu, European Union approval, HER2-positive metastatic breast cancer, pertuzumab