FDA Approves AstraZeneca, Daiichi Sankyo’s Enhertu for Unresectable or Metastatic Hormone Receptor-Positive, HER2-Low Breast Cancer

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The FDA has approved AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) as the first HER2-directed therapy for adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low, or HER2-ultralow metastatic breast cancer following progression on one or more endocrine therapies. As a result of the approval, AstraZeneca will be required to pay Daiichi Sankyo a total of $175 million in milestones. Enhertu is now approved in over 70 countries for HER2-low breast cancer, with regulatory reviews ongoing in additional regions.¹

According to AstraZeneca, approval was based on results from the DESTINY-Breast06 Phase III trial, which demonstrated the drug’s significant clinical benefits. The FDA previously granted the application with Priority Review and Breakthrough Therapy Designation.¹

“Endocrine therapy is typically used in the initial treatment of HR-positive metastatic breast cancer and following progression, subsequent chemotherapy is associated with poor outcomes. With a median progression-free survival exceeding one year and a response rate of more than 60 per cent, trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy,” said trial investigator Aditya Bardia, MD, MPH, program director, breast oncology, director, translational research integration, UCLA Health Jonsson Comprehensive Cancer Center, in a press release.

The global, randomized, open-label DESTINY-Breast06 trial evaluated the efficacy and safety of Enhertu against investigator’s choice of chemotherapy of capecitabine, paclitaxel, or nab-paclitaxel. Investigators enrolled 866 patients in Asia, Europe, Australia, North America, and South America. The trial’s primary endpoint was progression-free survival (PFS) as measured by blinded independent central review (BICR). Secondary endpoints included PFS as per BICR in the overall trial population, overall survival (OS) in the HER2-low patient population, and OS in the overall trial population.

Results found that Enhertu reduced the risk of disease progression or death by 36% and showed a median PFS of 13.2 months compared to 8.1 months with chemotherapy, with an objective response rate of 62.2%. The treatment’s safety profile was consistent with previous trials, with no new safety signals identified.¹

“Building on the practice-changing previous approvals for Enhertu, this new approval brings this important medicine to an earlier treatment setting and a broader patient population with HER2-expressing metastatic breast cancer. The approval also highlights the importance of testing metastatic breast cancer tumors for detectable staining with a standard IHC test to identify those who may be eligible for treatment with Enhertu following endocrine therapy,” said Dave Fredrickson, EVP, oncology hematology business unit, AstraZeneca, in the press release.

According to the American Cancer Society, it is estimated that around 316,950 new cases of invasive breast cancer will be diagnosed in women this year, with approximately 42,170 deaths. The average risk of a woman getting breast cancer during her lifetime is 13%. Currently, it is the second leading cause of cancer-related deaths in women. Between 1989 and 2022, deaths from breast cancer decreased by 44%, mainly due to the increasing number of cases that have been discovered early, increased awareness, and improved treatments.²

“Enhertu continues to redefine the classification and treatment of HR-positive metastatic breast cancer with important new data across the spectrum of HER2 expression. Today’s approval underscores our ongoing commitment to realizing the full potential of this innovative antibody drug conjugate and represents another paradigm shift in how certain breast cancers can be treated,” said Ken Keller, global head, oncology business, president, CEO, Daiichi Sankyo, in the press release.

References

1. Enhertu approved in the US as first HER2-directed therapy for patients with HER2-low or HER2-ultralow metastatic breast cancer following disease progression after one or more endocrine therapies. AstraZeneca. January 27, 2025. Accessed January 28, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html

2. Key Statistics for Breast Cancer. American Cancer Society. Accessed January 28, 2025. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html