FDA Approves Diagnostic Label Expansion for HR+, HER2–Ultra-Low Metastatic Breast Cancer

The FDA approved a label expansion for the Pathway anti-human epidermal growth receptor-2 (HER2)/neu Rabbit Monoclonal Primary Antibody as a diagnostic tool for patients with hormone receptor positive (HR+), HER2-ultralow metastatic breast cancer who may be eligible for treatment with fam-trastuzumab-deruxtecan-nxki (Enhertu; Daiichi-Sankyo, AstraZeneca). Trastuzumab-deruxtecan is approved for the treatment of unresectable or metastatic HR+, HER2-low, or HER2-ultra-low breast cancer.^1,2

HER2-ultralow now refers to patients who have low levels of HER2 expression, is lower than the existing HER2-low category. | Image Credit: Saiful52 | stock.adobe.com

Previously, HER2 status was categorized as either positive or negative, based on the level of HER2 expression. However, HER2-low status was introduced in 2022, so the approval can now identify a new patient population with HER2-ultra-low. HER2-ultra-low now refers to patients who have low levels of HER2 expression that are lower than the existing HER2-low category.²

“One in 8 women in the United States will face invasive breast cancer in their lifetime,” Matt Sause, CEO of Roche Diagnostics, said in the news release. “The rising incidence of metastatic breast cancer, particularly among younger populations, underscores the urgent need for new diagnostic options. The approval of our test for determining HER2-ultra-low status offers new hope to patients by providing a possible path to HER2-targeted treatment where none existed before, helping clinicians transform outcomes for many facing this challenging disease.”¹

Trastuzumab-deruxtecan previously received priority review and breakthrough therapy designation, with results from the DESTINY-Breast06 phase 3 trial showing a 36% reduction in the risk of disease progression or death compared with chemotherapy (HR 0.64; 95% CI: 0.54-0.76; P <.0001). The new indication allows for more individuals to receive treatment when therapeutic options are limited but still growing. The drug consists of a HER2 monoclonal antibody connected to a multiple topoisomerase I inhibitor, which shows effective antitumor activity and faster response time. It is also approved in multiple countries for other indications, which include patients with HER2+ breast cancer.²

“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,” Aditya Bardia, MD, MPH, investigator in the DESTINY-Breast06 trial, said in the news release. “With a median progression-free survival exceeding 1 year and a response rate of more than 60%, trastuzumab deruxtecan offers a potential new standard of care for patients with HR-positive, HER2-low, or HER2-ultra-low metastatic breast cancer following endocrine therapy.”³

REFERENCES

1. Roche receives FDA approval for the first companion diagnostic to identify patients with HER2-ultralow metastatic breast cancer eligible for Enhertu. News release. Roche. January 31, 2025. Accessed January 31, 2025. https://www.globenewswire.com/news-release/2025/01/31/3018924/0/en/Roche-receives-FDA-approval-for-the-first-companion-diagnostic-to-identify-patients-with-HER2-ultralow-metastatic-breast-cancer-eligible-for-ENHERTU.html

2. Halpern L. FDA Grants Trastuzumab Deruxtecan Approval for Endocrine-Treated Patients With Metastatic HR+, HER2-Low Breast Cancer. Pharmacy Times. January 28, 2025. Accessed January 31, 2025. https://www.pharmacytimes.com/view/fda-grants-trastuzumab-deruxtecan-approval-for-endocrine-treated-patients-with-metastatic-hr-her2-low-breast-cancer

3. AEnhertu 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. News Release. AstraZeneca. January 27, 2025. Accessed January 31, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html