AstraZeneca, Daiichi Sankyo ADC Enhertu upgraded to first-line breast cancer drug
Enhertu, a targeted cancer therapy from a partnership between AstraZeneca and Daiichi Sankyo, can now be used as a first-line treatment in cases of advanced breast cancer, making it the first newly approved treatment option in a decade.
Enhertu targets HER2, a protein that can be overexpressed on the surface of cancer cells. Expanded regulatory approval is important for breast cancer patients because HER2 makes tumors more aggressive and more difficult to control, so many patients do not live long enough to receive second-line treatments. The regulatory decision announced Monday covers the treatment of adults with HER2-positive unresectable or metastatic breast cancer. The FDA also approved two companion diagnostics to select patients eligible for treatment with the drug, which is part of the antibody-drug conjugate (ADC) class of therapies.
Dave Fredrickson, executive vice president of AstraZeneca's Oncology Hematology business unit, said in a prepared statement: “With this approval, we will bring Enhertu to the earliest treatment of HER2-positive metastatic breast cancer, where optimizing efficacy has an important impact on long-term outcomes.”
The standard first-line treatment for HER2-positive breast cancer is a three-drug regimen of taxanes, trastuzumab (trade name Herceptin), and pertuzumab (Perjeta)—the combination is often abbreviated THP. Enhertu's new approval is based on results from a three-arm Phase 3 study that randomly assigned patients to receive Enhertu, Enhertu plus Perjeta, or THP.
With the primary objective of measuring progression-free survival, the median survival in the Enhertu plus Perjeta group was 40.7 months, while the median survival in the THP group was 26.9 months. At the time of this analysis, overall survival was not yet mature, and 126 deaths were reported in both study groups. Detailed results were presented at the American Society of Clinical Oncology's annual meeting earlier this year and published in the New England Journal of Medicine.
The FDA approved Enhertu for use in first-line treatment, including with Perjeta. ADC was initially approved as a third-line treatment for HER2-positive breast cancer in 2019 and upgraded to second-line treatment in 2022. When the company announced Enhertu's new approval, Dr. Sara Tolaney, chief of breast oncology at Dana-Farber Cancer Institute and principal investigator on the drug's pivotal study, said Enhertu combined with Perjeta should become the new standard of care for first-line treatment of HER2-positive metastatic breast cancer.
Enhertu was discovered by Daiichi Sankyo. AstraZeneca and Daiichi Sankyo began collaborating on the ADC in 2019, before the drug received its first FDA approval. The two companies share the development and commercialization of Enhertu globally except in Japan, where Daiichi Sankyo owns all rights to the drug. In 2024, partners reported total Enhertu sales of $3.7 billion, an increase of more than 46% from the previous year.
Daiichi Sankyo said AstraZeneca will pay a $150 million milestone payment for Enhertu following its U.S. approval for first-line treatment of unresectable or metastatic HER2-positive breast cancer.
Public domain image courtesy of the National Cancer Institute
