AstraZeneca’s Enhertu EU Approval: Enhertu Plus Pertuzumab Cleared as First-Line Therapy for HER2-Positive Metastatic Breast Cancer

Enhertu EU Approval declared on 1 September 2026 as the European Commission cleared Enhertu (trastuzumab deruxtecan) in combination with pertuzumab for the first-line treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. The decision, developed jointly by AstraZeneca and Daiichi Sankyo, follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use and marks the first new first-line regimen for this patient population in more than a decade. The Enhertu EU approval is grounded in results from the DESTINY-Breast09 Phase III trial, presented at the 2025 American Society of Clinical Oncology Annual Meeting and later published in The New England Journal of Medicine.

In DESTINY-Breast09, Enhertu combined with pertuzumab reduced the risk of disease progression or death by 44% compared with a taxane, trastuzumab and pertuzumab (THP) regimen, the long-standing standard of care. The hazard ratio was 0.56 (95% CI 0.44-0.71; p<0.00001). Median progression-free survival reached 40.7 months with the Enhertu combination versus 26.9 months with THP, as assessed by blinded independent central review. That gap of nearly 14 months underpins much of the enthusiasm surrounding the Enhertu EU approval, since progression-free survival exceeding three years represents one of the longest reported outcomes yet in first-line HER2-positive metastatic breast cancer. Investigators noted the safety profile of the combination was consistent with the known profiles of each individual treatment, with no new safety concerns identified during the trial.

HER2-positive metastatic breast cancer affects 15% to 20% of the roughly 2.4 million breast cancer cases diagnosed worldwide each year, and most patients on THP still experience disease progression within about two years. Nearly one in three patients receive no further treatment after first-line therapy due to progression or death, underscoring why the Enhertu EU approval is being described as a shift in the treatment paradigm. In Europe alone, an estimated 540,000 breast cancer cases were diagnosed in 2024, with more than 140,000 deaths, and only around 30% of patients with metastatic disease are expected to survive five years following diagnosis.

Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital and the Vall d’Hebron Institute of Oncology in Barcelona, a steering committee investigator on DESTINY-Breast09, said maintaining disease control for as long as possible in the first-line setting remains a critical treatment goal for these patients, and that the combination 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 Enhertu EU approval brings the therapy to patients earlier in their disease course and that it “sets a new benchmark for progression-free survival” in the first-line setting.

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Enhertu EU Approval: Inside the DESTINY-Breast09 Trial Design

DESTINY-Breast09 is a global, multicentre, randomised, open-label Phase III trial that enrolled 1,157 patients across sites in Africa, Asia, Europe, North America and South America. Participants were randomised 1:1:1 to receive Enhertu monotherapy with a pertuzumab-matching placebo, Enhertu in combination with pertuzumab, or THP. Randomisation was stratified by prior treatment status (de novo metastatic disease versus progression from early-stage disease), hormone receptor status and PIK3CA mutation status. The trial’s primary endpoint is progression-free survival by blinded independent central review in both the Enhertu monotherapy and combination arms, while secondary endpoints include investigator-assessed progression-free survival, overall survival, overall response rate, duration of response, pharmacokinetics and safety. The Enhertu monotherapy versus THP comparison remains blinded to patients and investigators and will continue to a final progression-free survival analysis. This trial architecture is the evidentiary backbone behind the Enhertu EU approval granted by the European Commission.

Based on the DESTINY-Breast09 results, Enhertu plus pertuzumab has already been added to the ESMO Clinical Practice Guidelines as a Category IA first-line option for metastatic HER2-positive breast cancer, regardless of hormone receptor status. The Enhertu EU approval also follows a related tumour-agnostic approval granted roughly two months earlier, according to Daiichi Sankyo’s Ken Keller, Global Head of Oncology Business and President and CEO of Daiichi Sankyo, Inc., who said the milestone reflects the company’s goal of bringing the medicine to more eligible patients as quickly as possible.

The Enhertu EU approval also triggers a financial obligation under the companies’ collaboration agreement: AstraZeneca owes Daiichi Sankyo a $100 million milestone payment tied specifically to the first-line unresectable or metastatic HER2-positive breast cancer indication. Sales of Enhertu across most EU territories are recognised by Daiichi Sankyo rather than AstraZeneca, consistent with the terms the two companies established when they entered their global collaboration in March 2019. That agreement also covers Datroway (datopotamab deruxtecan), added via a separate collaboration in July 2020, with Daiichi Sankyo retaining exclusive rights to both antibody-drug conjugates in Japan and responsibility for their manufacturing and supply.

Enhertu EU Approval Adds to a Growing Global Label

Enhertu plus pertuzumab is now approved as a first-line treatment for unresectable or metastatic HER2-positive breast cancer in more than 40 countries and regions worldwide, and Enhertu alone carries authorisations in more than 100 countries and regions for second-line HER2-positive disease following the DESTINY-Breast03 trial. Enhertu is also approved in more than 75 countries and regions for hormone receptor-positive, HER2-low or HER2-ultralow disease under DESTINY-Breast06, in more than 100 countries and regions for HER2-low disease following DESTINY-Breast04, in more than 80 countries and regions for HER2-mutant non-small cell lung cancer, in more than 90 countries and regions for HER2-positive gastric or gastroesophageal junction adenocarcinoma, and in more than 45 countries and regions for HER2-positive solid tumours under a pan-tumour indication.

Enhertu remains under EU review for patients with residual invasive HER2-positive disease after neoadjuvant treatment, based on data from the DESTINY-Breast05 trial, and a broader clinical development programme continues to evaluate the medicine as a monotherapy and in combination across multiple HER2-targetable cancers. AstraZeneca has said it wants to expand Enhertu’s role into earlier lines of breast cancer treatment while also advancing other assets such as Truqap, Datroway and camizestrant in the hormone receptor-positive setting, reflecting how the Enhertu EU approval fits into a wider oncology strategy.

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DESTINY-Breast09 Efficacy Data (Enhertu + Pertuzumab vs. THP)

Enhertu Global Approval Status by Indication