By VETTAPHARMA reporter – Derek Roche: AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) plus pertuzumab has been approved in the European Union (EU) as a first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer. The approval makes the regimen the first new treatment option in more than a decade for this setting, according to the companies.
The European Commission approval is based on results from the global, multicentre, randomised, open-label DESTINY-Breast09 Phase III trial. The study evaluated Enhertu alone or in combination with pertuzumab against standard-of-care taxane, trastuzumab and pertuzumab (THP) in patients who had not received prior chemotherapy or HER2-targeted therapy, or whose prior neoadjuvant or adjuvant HER2-targeted treatment had ended more than six months before advanced or metastatic disease diagnosis.
In the combination arm, Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% versus THP, with a hazard ratio of 0.56 (95% CI, 0.44–0.71; p<0.00001). Median progression-free survival reached 40.7 months with Enhertu plus pertuzumab compared with 26.9 months with THP, as assessed by blinded independent central review.
DESTINY-Breast09 enrolled 1,157 patients across sites in Africa, Asia, Europe, North America and South America. Patients were randomised 1:1:1 to Enhertu monotherapy, Enhertu plus pertuzumab, or THP, with randomisation stratified by prior treatment, hormone receptor status and PIK3CA mutation status. Progression-free survival assessed by blinded independent central review was the primary endpoint, while secondary endpoints included investigator-assessed progression-free survival, overall survival, overall response rate, duration of response, pharmacokinetics and safety.
The safety profile of Enhertu plus pertuzumab was consistent with the known profiles of the individual treatments, with no new safety concerns identified.
The approval could change the first-line treatment landscape for HER2-positive metastatic breast cancer, where THP has been the standard of care for more than a decade. The source notes that most patients experience disease progression within two years of first-line THP treatment, while approximately one in three patients do not receive subsequent treatment because of disease progression or death.
The European Society for Medical Oncology has included Enhertu plus pertuzumab in its Clinical Practice Guidelines as a Category IA first-line treatment option for metastatic HER2-positive breast cancer, regardless of hormone receptor status.
For patients, the approval brings the Enhertu-based combination into the first-line setting in the EU, with the trial demonstrating a median progression-free survival exceeding three years. HER2-positive metastatic breast cancer affects an estimated 15% to 20% of patients with metastatic breast cancer and is described in the source as an aggressive disease driven by HER2 overexpression or amplification.
The approval also carries a financial milestone for the collaboration. AstraZeneca will pay Daiichi Sankyo $100 million following the EU approval for the first-line unresectable or metastatic HER2-positive breast cancer indication. Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo.
Enhertu is a HER2-directed antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. The medicine uses Daiichi Sankyo’s DXd ADC technology, combining a HER2 monoclonal antibody with a topoisomerase I inhibitor payload through cleavable linkers.
The companies are continuing a global clinical development programme evaluating Enhertu as a monotherapy, combination therapy or sequential treatment across multiple HER2-targetable cancers. In breast cancer, the companies are also expanding the medicine into earlier lines of treatment and additional settings.
Quick FAQs
1. What is the disease condition?
HER2-positive metastatic breast cancer is an aggressive form of breast cancer driven by HER2 overexpression or amplification.
2. What is the study/trial?
DESTINY-Breast09 is a global, multicentre, randomised, open-label Phase III trial evaluating Enhertu alone or with pertuzumab versus THP as first-line treatment.
3. What did Enhertu plus pertuzumab achieve?
The combination reduced the risk of disease progression or death by 44% versus THP.
4. What was the median progression-free survival?
Median progression-free survival was 40.7 months with Enhertu plus pertuzumab versus 26.9 months with THP.
5. What is the regulatory status in Europe?
The European Commission approved Enhertu plus pertuzumab for first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer.
6. What is the financial impact of the EU approval?
AstraZeneca will pay Daiichi Sankyo a $100 million milestone for the first-line indication.
