As reported on Business Wire, the European Commission has approved trastuzumab deruxtecan (Enhertu) in combination with pertuzumab for the first-line treatment of adults with unresectable or metastatic HER2-positive breast cancer. The decision introduces the first new frontline treatment regimen for this patient population in more than a decade and follows positive findings from the phase 3 DESTINY-Breast09 trial.
Developed by Daiichi Sankyo and AstraZeneca, Enhertu is a HER2-targeted antibody-drug conjugate designed to deliver chemotherapy directly to cancer cells expressing HER2. The European approval applies to patients whose tumors are classified as HER2-positive by immunohistochemistry (IHC 3+) or in situ hybridization (ISH+).
DESTINY-Breast09 Demonstrated Significant Progression-Free Survival Benefit
The approval was supported by results from the DESTINY-Breast09 study, which evaluated Enhertu plus pertuzumab against the longstanding standard regimen of taxane, trastuzumab, and pertuzumab (THP) in previously untreated patients with metastatic HER2-positive breast cancer.
Among 383 participants, the investigational combination reduced the risk of disease progression or death by 44% compared with THP. Median progression-free survival reached 40.7 months for patients receiving Enhertu plus pertuzumab, versus 26.9 months for those treated with the standard regimen.
The study also reported higher tumor response rates with the new combination. Confirmed objective responses were observed in 85.1% of patients receiving Enhertu and pertuzumab compared with 78.6% of patients treated with THP.
Researchers noted that patients enrolled in the trial had not previously received chemotherapy or HER2-directed therapy for metastatic disease, although some had been treated with HER2-targeted therapies in the neoadjuvant or adjuvant setting more than six months before developing advanced disease.
Potential Shift in the First-Line Standard of Care
Clinical investigators involved in DESTINY-Breast09 described the findings as a meaningful advance for patients with HER2-positive metastatic breast cancer, a disease in which prolonged disease control remains a primary treatment objective.
With progression-free survival extending beyond three years in the study, the Enhertu-pertuzumab regimen may establish a new benchmark in the frontline setting and could reshape treatment algorithms across Europe.
Reflecting the strength of the evidence, the European Society for Medical Oncology (ESMO) has already incorporated the combination into its Clinical Practice Guidelines as a Category IA first-line treatment option for metastatic HER2-positive breast cancer, regardless of hormone receptor status.
Safety Findings Consistent With Known Profiles
Investigators reported no unexpected safety signals with the combination therapy. The adverse-event profile generally aligned with the known effects of Enhertu and pertuzumab when used individually.
In a pooled analysis of 431 patients treated across two clinical studies, the most common grade 3 or 4 adverse events included neutropenia, hypokalemia, anemia, diarrhea, fatigue, thrombocytopenia, elevated liver enzymes, leukopenia, and nausea. Less frequent but clinically significant events included reduced cardiac ejection fraction and febrile neutropenia.
Grade 5 adverse reactions occurred in 1.6% of patients. Reported fatal events included pneumonia, interstitial lung disease (ILD)/pneumonitis, dyspnea, and febrile neutropenia. As with previous Enhertu studies, monitoring for ILD remains an important aspect of patient management.
Expanding Global Reach for Enhertu
The European authorization marks the second EU approval for Enhertu within a two-month period, following a recent tumor-agnostic indication. Company representatives from Daiichi Sankyo and AstraZeneca emphasized that the new approval enables patients to receive the therapy earlier in the metastatic disease course, where maximizing treatment benefit may have the greatest impact on long-term outcomes.
Enhertu plus pertuzumab is now approved as a first-line treatment for HER2-positive metastatic breast cancer in more than 40 countries and regions worldwide. Meanwhile, the therapy is also under regulatory review in Europe for patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant HER2-directed treatment, based on findings from the DESTINY-Breast05 trial.
Key Takeaway
The EU approval of Enhertu combined with pertuzumab represents a major development in HER2-positive metastatic breast cancer treatment. Backed by phase 3 evidence showing a substantial reduction in disease progression risk and median progression-free survival exceeding three years, the regimen is poised to become a leading frontline treatment option and potentially redefine standards of care across Europe.
