The FDA has granted approval to Roche's PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody test for identifying patients with hormone receptor (HR)-positive, HER2-ultralow metastatic breast cancer who may be eligible for treatment with ENHERTU (fam-trastuzumab deruxtecan-nxki). This approval marks a significant advancement in personalized medicine for breast cancer, offering new hope for patients with limited treatment options.
This label expansion for Roche's PATHWAY HER2 (4B5) test, already approved for HER2-low status since 2022, now includes the identification of patients with HER2-ultralow expression. HER2-ultralow refers to a level of HER2 expression even lower than the existing HER2-low category. Approximately 20-25% of HR-positive, HER2-negative breast cancer patients may be classified as HER2-ultralow, potentially expanding the pool of patients who could benefit from targeted therapies.
Clinical Evidence from DESTINY-Breast06 Trial
The approval is supported by data from the phase 3 DESTINY-Breast06 trial, which evaluated the efficacy and safety of ENHERTU in patients with HER2-low and HER2-ultralow metastatic breast cancer. The trial demonstrated a median progression-free survival (PFS) of 13.2 months with ENHERTU compared to 8.1 months with standard of care chemotherapy in the overall trial population. An exploratory analysis showed consistent results between patients with HER2-low and HER2-ultralow expression.
In the HER2-ultralow population, the median PFS was 13.2 months for T-DXd (n = 76) vs 8.3 months for chemotherapy (n = 75; HR, 0.78; 95% CI, 0.50-1.21).
Improving Diagnostic Accuracy and Treatment Decisions
According to Matt Sause, CEO of Roche Diagnostics, "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." The PATHWAY HER2 (4B5) test, when used with the fully automated BenchMark IHC/ISH slide staining instrument, standardizes immunohistochemistry (IHC) processes, reducing human error and variability. The Roche HER2 (4B5) clone achieves consistently high proficiency assessment scores compared to other clones and demonstrates high concordance with HER2 FISH, empowering laboratories to employ the most widely adopted and reliable HER2-IHC primary antibody.
The Evolving Landscape of HER2 Testing
Prior to the introduction of HER2-low status in 2022, HER2 status was categorized as either "positive" or "negative" based on HER2 expression levels. The approval of the PATHWAY HER2 (4B5) test to identify HER2-ultralow patients marks a further refinement in HER2 testing, enabling more personalized treatment strategies for metastatic breast cancer. This evolution in HER2 interpretation allows for a more nuanced assessment of patient eligibility for HER2-targeted therapies like ENHERTU, potentially improving outcomes for a broader range of patients.
