The European Commission’s approval follows a positive opinion from the EMA’s Committee for Medicinal Products for Human Use and is based on the Phase III DESTINY-Breast09 trial, presented at the 2025 ASCO Annual Meeting and subsequently published in the New England Journal of Medicine.

In the trial, Enhertu plus pertuzumab cut the risk of disease progression or death by 44 percent compared with the current standard of care — a taxane, trastuzumab and pertuzumab (THP) — in patients who had not previously received chemotherapy or HER2-targeted therapy for advanced disease. Median progression-free survival reached 40.7 months with the new combination, against 26.9 months with THP, as assessed by blinded independent central review. The safety profile was consistent with what is already known for each individual treatment, with no new safety signals identified.

THP has been the first-line standard of care for HER2-positive metastatic breast cancer for more than a decade, and most patients on it still progress within two years. Based on the DESTINY-Breast09 results, the Enhertu-pertuzumab combination has already been added to the ESMO Clinical Practice Guidelines as a Category IA first-line option, regardless of hormone receptor status.

The approval also triggers a $100 million milestone payment from AstraZeneca to Daiichi Sankyo under the companies’ 2019 collaboration agreement. Enhertu, a HER2-directed antibody-drug conjugate discovered by Daiichi Sankyo and co-developed with AstraZeneca, is now approved with pertuzumab as a first-line treatment in more than 40 countries and regions worldwide.

Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital and the Vall d’Hebron Institute of Oncology in Barcelona, an investigator on the trial, said the combination represents:

“A significant therapeutic advance, with progression-free survival exceeding three years compared to approximately two years with the current standard of care.”

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval:

“Sets a new benchmark for progression-free survival in the first-line setting.”

Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., called it Enhertu’s second new EU indication in two months, following the recent tumour-agnostic approval, adding that it:

“Has the potential to reshape clinical practice in the first-line treatment setting for patients with HER2-positive metastatic breast cancer.”

Enhertu is also under EU review for patients with residual invasive HER2-positive disease after neoadjuvant treatment, based on data from the DESTINY-Breast05 trial.