FDA Approves AstraZeneca’s Enhertu Plus Pertuzumab As First-Line Treatment For HER2-Positive Metastatic Breast Cancer

AstraZeneca and Daiichi Sankyo have received U.S. FDA approval for Enhertu® (trastuzumab deruxtecan) in combination with pertuzumab as a first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer, as confirmed by an FDA-approved diagnostic test. The approval follows a Priority Review and Breakthrough Therapy Designation, underscoring the regimen’s clinical significance in this setting.

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.”

The decision is supported by data from the Phase III DESTINY-Breast09 trial, which were presented at the 2025 ASCO Annual Meeting and published in The New England Journal of Medicine. In the study, the Enhertu-pertuzumab combination demonstrated a 44% reduction in the risk of disease progression or death compared with standard therapy consisting of a taxane, trastuzumab and pertuzumab (THP).

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.”

Patients treated with Enhertu plus pertuzumab achieved a median progression-free survival of 40.7 months, compared with 26.9 months for those receiving THP. The improvement in progression-free survival was consistent across all predefined patient subgroups, reinforcing the robustness of the findings. The safety profile of the combination aligned with the known profiles of the individual therapies, with no new safety signals observed.

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.”

Enhertu is a HER2-directed DXd antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialised with AstraZeneca. The approval was granted through the FDA’s Real-Time Oncology Review programme and was also assessed under Project Orbis, with additional regulatory reviews ongoing in multiple international markets, including Switzerland and Singapore.