FDA Approves Expanded Label for Roche's Companion Diagnostic to Identify HER2-Ultralow Breast Cancer Patients Eligible for Enhertu

Roche has received FDA approval for a label expansion of its PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody test, which identifies patients with HR–positive, HER2-ultralow metastatic breast cancer (MBC) who may be eligible for treatment with Enhertu (trastuzumab deruxtecan; AstraZeneca and Daiichi Sankyo).¹ Last week, the FDA approved Enhertu as the first HER2-directed therapy for adults with unresectable or metastatic HR-positive, HER2-low, or HER2-ultralow MBC who experienced disease progression following one or more endocrine therapies.2 Roche noted that between 20% and 25% of patients with HR-positive, HER2-negative breast cancer can be defined as HER2-ultralow.

“One in eight women in the United States will face invasive breast cancer in their lifetime,” said Matt Sause, CEO of Roche Diagnostics, in a press 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-ultralow 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

The expanded label for the PATHWAY anti-HER2 (4B5) test now includes the identification of patients designated as "HER2-ultralow,” which is individuals with extremely low HER2 expression levels that are lower than the current HER2-low category. Prior to HER2-low status being introduced in 2022, HER2 status was defined as being either positive or negative based HER2 expression levels.¹

The PATHWAY anti-HER2/neu test is utilized in combination with the BenchMark IHC/ISH slide staining instrument. This process standardizes immunohistochemistry practices to lower the possibility of human error and variability. According to Roche, the system produces consistently high proficiency scores that are concordant with HER2 FISH. The test was used as part of the DESTINY-Breast06 Phase III trial, which was the basis of the approval for Enhertu.

DESTINY-Breast06 was a global, randomized, open-label trial that analyzed the efficacy and safety of Enhertu vs. investigator’s choice of chemotherapy with capecitabine, paclitaxel, or nab-paclitaxel. A total of 866 patients were enrolled across 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), with secondary endpoints that 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.

Trial data show that Enhertu lowered the risk of disease progression or death by 36% with a median PFS of 13.2 months vs. 8.1 months in patients administered chemotherapy. Results also showed an objective response rate of 62.2%.

“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. With a median progression-free survival exceeding one 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-ultralow metastatic breast cancer following endocrine therapy,” trial investigator Aditya Bardia, MD, MPH, program director, breast oncology, director, translational research integration, UCLA Health Jonsson Comprehensive Cancer Center, said in a press release.²

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 30, 2025. Accessed February 4, 2025. https://www.roche.com/media/releases/med-cor-2025-01-31

2. 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 February 4, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html