European Commission approves Enhertu + pertuzumab for the 1st-line treatment of patients with HER2-positive metastatic breast cancer – AstraZeneca + Daiichi Sankyo

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) in combination with pertuzumab has been approved in the European Union (EU) for the 1st-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer.
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency and is based on results from the DESTINY-Breast09 Phase III trial presented at the 2025 American Society of Clinical Oncology Annual Meeting and subsequently published in The New England Journal of Medicine.

Cristina Saura, MD, PhD, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, steering committee member and investigator for the DESTINY-Breast09 trial, said: “For patients diagnosed with HER2-positive metastatic breast cancer, maintaining disease control for as long as possible in the first-line setting is a critical treatment goal. The combination of trastuzumab deruxtecan and pertuzumab represents a significant therapeutic advance, with progression-free survival exceeding three years compared to approximately two years with the current standard of care, and has the potential to become the new first-line standard of care.”

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “This 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. HER2-positive metastatic breast cancer is an aggressive disease, so to give patients the best chance of improving long-term outcomes, it is critical to initiate effective

 

HER2-directed therapy early and continue treatment for as long as patients benefit.”

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: “This milestone marks the second new indication for Enhertu in the EU in just two months following the recent tumour agnostic approval, underscoring our goal to bring this medicine to more eligible patients as quickly as possible. This approval of Enhertu in combination with pertuzumab has the potential to reshape clinical practice in the first-line treatment setting for patients with HER2-positive metastatic breast cancer.”

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

The safety profile of Enhertu plus pertuzumab was consistent with the known profiles of each individual treatment with no new safety concerns identified.

Based on the results of DESTINY-Breast09, Enhertu in combination with pertuzumab has been included in the ESMO Clinical Practice Guidelines as a Category IA 1st-line treatment option for patients with metastatic HER2-positive breast cancer, regardless of hormone receptor (HR) status.

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

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Financial considerations
Following this approval in the EU, an amount of $100 million is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the 1st-line unresectable or metastatic HER2-positive breast cancer indication. Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo.

DESTINY-Breast09
DESTINY-Breast09 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) either alone or in combination with pertuzumab versus standard of care THP as 1st-line treatment in patients with HER2-positive metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy or had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before the diagnosis of advanced or metastatic disease. Patients were randomised 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomisation was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), HR status and PIK3CA mutation status. The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, overall response rate, duration of response, pharmacokinetics and safety. The investigational arm assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis. DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America.

Citation: Tolaney SM, Jiang Z, Zhang Q et al. Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2025 Oct 29. doi: 10.1056/NEJMoa2508668.