The recommendation is based on findings from the Phase III DESTINY-Breast09 study, which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and later published in The New England Journal of Medicine. If approved by the European Commission, the regimen could become a new frontline treatment option for patients with this aggressive form of breast cancer.

Significant Improvement Over Current Standard of Care

DESTINY-Breast09 compared Enhertu plus pertuzumab with the longstanding standard first-line regimen consisting of a taxane chemotherapy, trastuzumab and pertuzumab (THP). The trial enrolled patients with HER2-positive metastatic breast cancer who had not previously received treatment for advanced disease or whose earlier HER2-directed therapy had been completed more than six months before recurrence.

Results showed that the Enhertu-based combination reduced the risk of disease progression or death by 44% compared with THP. Median progression-free survival reached 40.7 months in the investigational arm, versus 26.9 months among patients receiving standard therapy, representing an improvement of more than one year.

The progression-free survival benefit was observed consistently across multiple patient subgroups, including those defined by hormone receptor status, disease presentation and PIK3CA mutation status.

Safety Profile Remains Consistent

Investigators reported that the safety findings for the combination were in line with the established safety profiles of Enhertu and pertuzumab individually. No unexpected adverse events or new safety concerns were identified during the study.

These findings suggest that the enhanced efficacy was achieved without introducing previously unrecognized safety risks.

Unmet Need in HER2-Positive Metastatic Disease

HER2-positive breast cancer accounts for approximately 15% to 20% of metastatic breast cancer cases and is characterized by overexpression or amplification of the HER2 protein, which promotes tumour growth. Although targeted therapies have substantially improved outcomes over the past decade, many patients still experience disease progression within two years of beginning first-line treatment.

Additionally, a substantial proportion of patients are unable to receive subsequent therapies because of disease progression or death, highlighting the importance of achieving durable disease control early in the treatment pathway.

The prolonged progression-free survival observed in DESTINY-Breast09 suggests that introducing Enhertu earlier in treatment may help extend the period during which patients can keep their disease under control.

About the DESTINY-Breast09 Trial

DESTINY-Breast09 is a global, randomized, open-label Phase III study involving 1,157 patients across sites in Africa, Asia, Europe, North America and South America.

Participants were assigned to one of three groups:

• Enhertu plus pertuzumab
• Enhertu alone
• Standard THP therapy

The primary endpoint is progression-free survival assessed by blinded independent central review. Additional endpoints include overall survival, objective response rate, duration of response and safety. The monotherapy comparison arm remains ongoing and blinded pending final analysis.

Expanding Role for Enhertu

Enhertu is a HER2-targeted antibody-drug conjugate developed by Daiichi Sankyo and jointly commercialized with AstraZeneca. The therapy combines a HER2-directed monoclonal antibody with a potent topoisomerase I inhibitor payload using Daiichi Sankyo’s proprietary DXd technology.

The drug is already approved in numerous countries for several HER2-expressing cancers, including metastatic HER2-positive breast cancer, HER2-low breast cancer, non-small cell lung cancer, gastric cancer and certain HER2-positive solid tumours. The combination of Enhertu and pertuzumab has already secured first-line approvals for HER2-positive metastatic breast cancer in the United States, Switzerland and several other markets.

In Europe, regulators are also reviewing Enhertu for patients with residual invasive HER2-positive breast cancer following neoadjuvant HER2-directed treatment, based on results from the DESTINY-Breast05 trial.

Looking Ahead

The CHMP opinion marks another important milestone in the evolution of HER2-targeted therapy. With progression-free survival extending beyond three years in DESTINY-Breast09, the Enhertu-pertuzumab combination has demonstrated the potential to reshape initial treatment strategies for metastatic HER2-positive breast cancer.

A final decision from the European Commission is now awaited. If approved, the regimen could establish a new benchmark for first-line treatment in a patient population that continues to face significant challenges despite advances in targeted therapy.