AstraZeneca and Daiichi Sankyo have announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review to the supplemental Biologics License Application (sBLA) for Enhertu (trastuzumab deruxtecan) in combination with pertuzumab as a first-line treatment for adult patients with unresectable or metastatic HER2-positive breast cancer.
The application is based on data from the Phase III DESTINY-Breast09 trial, which demonstrated that Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% compared to the current standard regimen THP (trastuzumab, pertuzumab and a taxane). Median progression-free survival exceeded three years in the Enhertu combination arm versus 26.9 months with THP.
DESTINY-Breast09 trial results
- Progression-free survival (PFS): 40.7 months with Enhertu + pertuzumab vs. 26.9 months with THP
- Hazard ratio: 0.56; 95% CI 0.44–0.71; p<0.00001
- Objective response rate (ORR): 85.1% vs. 78.6%
- Complete responses: 58 with Enhertu + pertuzumab vs. 33 with THP
- Safety: No new safety signals identified
The FDA Priority Review reflects the potential for this combination to provide a significant improvement over existing therapies. A decision is expected in the first quarter of 2026 under the Prescription Drug User Fee Act (PDUFA).
Clinical impact
HER2-positive metastatic breast cancer is an aggressive form of the disease that accounts for approximately 15–20% of breast cancer cases. In the US, around 10,000 patients are treated each year in the first-line metastatic HER2-positive setting. Despite current treatments, many patients progress within two years, and up to one-third do not receive second-line therapy.
Expert perspectives
Susan Galbraith, Executive Vice President, Oncology R&D at AstraZeneca, said:
The DESTINY-Breast09 trial showed that treating patients with HER2-positive metastatic breast cancer with Enhertu in combination with pertuzumab until progression in the first-line setting produced a new landmark of more than 40 months for progression-free survival and nearly doubled the number of patients with no evidence of disease on imaging. This marks the first major evolution in treatment in this first-line setting in more than a decade.
Ken Takeshita, Global Head, R&D at Daiichi Sankyo, added:
Enhertu in combination with pertuzumab delayed disease progression for more than three years compared to around two years with current standard of care. Receiving Priority Review moves us closer to offering Enhertu to patients even earlier in the metastatic treatment pathway as a potential new first-line treatment option.
