AstraZeneca-Daiichi Sankyo Enhertu Combo wins USFDA approval for 1st-line HER2-Positive Metastatic Breast Cancer

The approval follows Priority Review and Breakthrough Therapy Designation by the FDA and is based on the results of the DESTINY-Breast09 Phase III trial. The data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.

Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute and principal investigator for the trial, said, “Trastuzumab deruxtecan plus pertuzumab is the only 1st-line treatment approved in more than a decade to demonstrate a statistically significant improvement in progression-free survival over the current standard regimen for patients with HER2-positive metastatic breast cancer. With a median progression-free survival exceeding three years, versus approximately two years with THP, trastuzumab deruxtecan combined with pertuzumab should become a new 1st-line standard of care in this setting.”

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said, “With this approval, we are bringing Enhertu to the earliest setting for HER2-positive metastatic breast cancer, where optimising efficacy has an important impact on long‑term outcomes. The treatment approach with Enhertu plus pertuzumab in DESTINY-Breast09 sets a new benchmark of more than three years without disease progression or death for patients in this setting.”

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, said, “Since its initial approval six years ago, Enhertu has transformed the treatment of HER2-positive metastatic breast cancer. With this approval of Enhertu in the 1st-line HER2-positive metastatic setting, Enhertu once again offers significant improvements in progression-free survival and has practice-changing potential when used in combination with pertuzumab.”

In the trial, Enhertu in combination with pertuzumab reduced the risk of disease progression or death by 44% versus a taxane, trastuzumab and pertuzumab (THP) (based on a hazard ratio of 0.56; 95% confidence interval [CI] 0.44-0.71; p<0.0001) as a 1st-line treatment for patients with HER2-positive metastatic breast cancer. Median progression-free survival (PFS) was 40.7 months with Enhertu plus pertuzumab compared to 26.9 months for THP. The PFS benefit for Enhertu plus pertuzumab versus THP was consistent across subgroups.

The safety profile of Enhertu plus pertuzumab in DESTINY-Breast09 was consistent with the known profiles of each individual therapy with no new safety concerns identified.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

This application was approved under the FDA’s Real-Time Oncology Review (RTOR), an initiative by the FDA to ensure safe and effective treatments are available to patients as early as possible.

This US regulatory submission was also reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, the Enhertu plus pertuzumab 1st-line regimen is under review by Switzerland’s Swissmedic (SMC) and Singapore's Health Sciences Authority (HSA). Separate regulatory applications are also under review in other countries.

Following this approval in the US, an amount of $150m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the 1st-line unresectable or metastatic HER2-positive breast cancer indication. Sales of Enhertu in the US are recognised by Daiichi Sankyo.