The European Commission has approved the combination of Enhertu and Pertuzumab for the treatment of adult patients with HER2-positive metastatic breast cancer, announced by AstraZeneca and Daiichi Sankyo.
This approval introduces the first new first-line treatment regimen in this setting in over a decade, providing patients with an alternative to long-standing standards of care. The decision is supported by data from the DESTINY-Breast09 Phase 3 trial.
The DESTINY-Breast09 trial enrolled 1,157 patients globally, comparing the Enhertu and Pertuzumab combination against the established standard of care—taxane, trastuzumab, and pertuzumab (THP). The combination reduced the risk of disease progression or death by 44% compared to THP, yielding a hazard ratio of 0.56 (95% CI: 0.44-0.71; p<0.00001).
Median progression-free survival surpassed three years at 40.7 months, compared to 26.9 months with THP. The confirmed objective response rate also improved, reaching 85.1% versus 78.6% with THP.
Investigators highlighted the critical importance of sustaining disease control in the first-line setting, noting that this regimen has the potential to become the new standard of care. Dr. Cristina Saura, MD, PhD, of Vall d’Hebron University Hospital, emphasized that the combination achieved progression-free survival beyond three years, compared to approximately two years with the current standard.
Safety data from the trial indicated that the combination’s profile aligned with the known effects of each individual drug, with no new safety concerns identified. Grade 3 or 4 adverse reactions included neutropenia (24.8%), anemia (10.7%), and diarrhea (7.4%), while grade 5 events occurred in 1.6% of patients, including pneumonia and interstitial lung disease.
The approval also carries financial implications, triggering a $100 million milestone payment from AstraZeneca to Daiichi Sankyo under their collaboration agreement. Daiichi Sankyo will recognize sales in most EU territories.
HER2-positive metastatic breast cancer is an aggressive disease driven by the overexpression of the HER2 protein, affecting 15-20% of patients and often leaving them with limited treatment options once the cancer spreads. Enhertu, an antibody-drug conjugate, delivers chemotherapy directly to cancer cells by targeting HER2, while Pertuzumab blocks HER2 signaling. Together, the combination enhances outcomes by merging targeted delivery with pathway inhibition.
This milestone represents the second EU approval for Enhertu in just two months, reinforcing AstraZeneca and Daiichi Sankyo’s dedication to advancing targeted therapies and transforming clinical practice in HER2-positive breast cancer.