AstraZeneca and Daiichi Sankyo’s Enhertu in combination with pertuzumab has secured European Union approval as a first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer, potentially reshaping frontline treatment for a disease where the existing standard has stood for more than a decade.

 

The European Commission approval is based on results from the Phase III DESTINY-Breast09 trial, which showed that the Enhertu-pertuzumab combination cut the risk of disease progression or death by 44% compared with the existing taxane, trastuzumab and pertuzumab (THP) regimen.

 

Median progression-free survival reached 40.7 months with Enhertu plus pertuzumab, compared with 26.9 months for THP — extending disease control by more than a year and taking median progression-free survival beyond three years.

 

Cristina Saura, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, 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.”

 

The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

 

“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,” said Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca.

 

The companies said the safety profile of Enhertu plus pertuzumab was consistent with the known safety profiles of the individual treatments, with no new safety concerns identified.

 

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.”

 

DESTINY-Breast09 enrolled 1,157 patients across Africa, Asia, Europe, North America and South America. The global Phase III trial evaluated Enhertu alone or in combination with pertuzumab against THP in patients who had not previously received chemotherapy or HER2-targeted therapy for metastatic disease, or who had received neoadjuvant or adjuvant HER2-targeted therapy more than six months before developing advanced or metastatic disease.

 

Patients were randomised to receive Enhertu monotherapy, Enhertu plus pertuzumab, or THP. The primary endpoint was progression-free survival assessed by blinded independent central review.

 

The Enhertu-plus-pertuzumab arm delivered a hazard ratio of 0.56, with a 95% confidence interval of 0.44-0.71 and p<0.00001, translating into a 44% reduction in the risk of progression or death versus THP.

 

The results have already influenced clinical guidelines. Based on DESTINY-Breast09, the Enhertu-pertuzumab combination has been included in the ESMO Clinical Practice Guidelines as a Category IA first-line treatment option for metastatic HER2-positive breast cancer, regardless of hormone receptor status.

 

HER2-positive metastatic breast cancer is an aggressive form of the disease driven by HER2 overexpression or gene amplification. Around 15% to 20% of patients with metastatic breast cancer are affected, and despite major advances in HER2-targeted therapy, prognosis remains poor.