Enhertu Plus Pertuzumab Granted Priority Review In The US As First-Line Treatment For HER2-Positive Metastatic Breast Cancer

AstraZeneca and Daiichi Sankyo announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to their 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. Priority Review is granted to medicines that, if approved, could offer significant improvements over existing treatments by demonstrating better safety, efficacy, or patient outcomes. The FDA action date under the Prescription Drug User Fee Act is expected in the first quarter of 2026. 

Enhertu was also recently granted Breakthrough Therapy Designation (BTD) in this setting, a program designed to expedite the development and review of therapies addressing serious conditions and unmet medical needs. HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 and affects approximately 15% to 20% of patients with metastatic breast cancer. Around 10,000 patients in the U.S. receive first-line treatment for HER2-positive metastatic breast cancer each year.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, stated that the DESTINY-Breast09 trial demonstrated that treating patients with Enhertu plus pertuzumab until progression in the first-line setting achieved a median progression-free survival of over 40 months and nearly doubled the number of patients with no evidence of disease on imaging. She highlighted that this represents the first major evolution in first-line treatment in more than a decade, in a setting where strong responses are crucial, as up to one-third of patients may not proceed to second-line therapy.

Ken Takeshita, Global Head of R&D at Daiichi Sankyo, noted that Enhertu in combination with pertuzumab delayed disease progression for over three years compared to around two years with current standard-of-care therapy. He added that receiving Priority Review brings the therapy closer to patients earlier in the metastatic treatment pathway as a potential first-line option. The sBLA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program, which allows the agency to assess components of an application before the full submission to expedite access to safe and effective cancer treatments. 

The application is based on results from the DESTINY-Breast09 Phase III trial, presented as a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. In the trial, Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% compared with taxane, trastuzumab, and pertuzumab (THP), with a hazard ratio of 0.56. Median progression-free survival was 40.7 months with Enhertu plus pertuzumab compared to 26.9 months for THP, with consistent benefits across patient subgroups. 

The confirmed objective response rate was 85.1% versus 78.6% with THP, including 58 complete responses compared to 33 with THP. The safety profile was consistent with the known profiles of each therapy, with no new safety concerns identified. Enhertu is a HER2-directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. It is already approved in more than 85 countries as a second-line treatment for patients with HER2-positive breast cancer, based on the results from the DESTINY-Breast03 Phase III trial.