The U.S. Food and Drug Administration (FDA) has approved trastuzumab deruxtecan (T-DXd) in combination with pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. The approval is based on results from the phase III DESTINY-Breast09 study, led by Dr. Sara Tolaney, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, presented at the 2025 ASCO Annual Meeting and published recently in the New England Journal of Medicine.
“T-DXd plus pertuzumab is the only first-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,” said Tolaney.
Sara Tolaney, MD, MPH
HER2-targeted therapies have improved outcomes dramatically for patients with metastatic HER2-positive breast cancer, with a median survival of more than five years. However, most patients experience progression of their disease within two years of treatment with the current first-line standard of care and approximately 30 percent of patients are unable to receive a second line of therapy.
The global, open-label DESTINY-Breast09 study randomized 383 patients to receive T-DXd plus pertuzumab and 387 to receive the standard of care THP. Median progression free survival with T-DXd plus pertuzumab was 40.7 months, compared to 26.9 months for patients who received the current standard of treatment. Fifteen percent of patients on the T-DXd combination experienced complete responses, in which their cancer disappeared. Progression free survival improvements were observed regardless of whether the patient had been newly diagnosed with metastatic disease or had a metastatic recurrence, and regardless of hormone receptor or PIK3CA mutation status.
“We are fortunate that we have an expanding array of effective HER2-directed therapies that have improved survival, but there is still meaningful room for progress,” says Tolaney. “Our goal is to optimize outcomes from the outset by selecting treatments with the greatest potential to delay disease progression, allowing patients to live longer and better lives.”