EU approves Enhertu plus pertuzumab as first new first line HER2 positive metastatic breast cancer regimen in over a decade

The European Commission has approved AstraZeneca and Daiichi Sankyo’s Enhertu, or trastuzumab deruxtecan, in combination with pertuzumab for the first line treatment of adults with unresectable or metastatic HER2 positive breast cancer.

The decision makes the combination the first new regimen approved in the EU for this treatment setting in more than a decade.

The approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use and is supported by data from the Phase III DESTINY Breast09 trial. Results 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, who served on the DESTINY Breast09 steering committee and was an investigator in the trial, said achieving durable disease control is a key objective when treating HER2 positive metastatic breast cancer in the first line setting. She said the trastuzumab deruxtecan and pertuzumab combination represents a meaningful therapeutic advance, with progression free survival extending beyond three years compared with about two years under the current standard of care, and could establish a new first line standard.

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval allows patients in the EU to receive Enhertu earlier in the metastatic disease course and establishes a new benchmark for progression free survival in this setting. He added that because HER2 positive metastatic breast cancer is aggressive, starting effective HER2 directed treatment early and continuing it while patients continue to benefit may help improve long term outcomes.

Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., said the decision represents the second new EU indication for Enhertu within two months, following its recent tumour agnostic approval. He said the latest approval could change clinical practice for patients receiving first line treatment for HER2 positive metastatic breast cancer.

In DESTINY Breast09, treatment with Enhertu plus pertuzumab lowered the risk of disease progression or death by 44% compared with a taxane combined with trastuzumab and pertuzumab, known as THP. The hazard ratio was 0.56, with a 95% confidence interval of 0.44 to 0.71 and a p value below 0.00001.

The study included patients with HER2 positive metastatic breast cancer who had not previously received chemotherapy or HER2 targeted treatment for metastatic disease. Patients who had received neoadjuvant or adjuvant HER2 targeted therapy were also eligible if more than six months had passed before their advanced or metastatic diagnosis.

Median progression free survival reached 40.7 months with Enhertu plus pertuzumab, compared with 26.9 months for THP, according to blinded independent central review.

No new safety concerns were identified, and the safety profile of the combination was consistent with the established profiles of Enhertu and pertuzumab individually.

Following the DESTINY Breast09 results, the ESMO Clinical Practice Guidelines have included Enhertu plus pertuzumab as a Category IA first line treatment option for metastatic HER2 positive breast cancer, irrespective of hormone receptor status.

Enhertu is also being reviewed in the EU for patients with HER2 positive breast cancer who have residual invasive disease after receiving neoadjuvant HER2 targeted therapy. That application is supported by findings from the DESTINY Breast05 trial.

Enhertu is a HER2 directed DXd antibody drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialised with AstraZeneca.

Under the companies’ collaboration agreement, AstraZeneca will make a $100 million milestone payment to Daiichi Sankyo following the EU approval for the first line unresectable or metastatic HER2 positive breast cancer indication. Daiichi Sankyo records sales of Enhertu across most EU markets.

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Related Topics and Keywords

AstraZeneca, Biopharma, breast cancer, Cancer, clinical trials, enhertu, eu approval, metastatic breast cancer, Oncology, pertuzumab