In the months leading up to the transformative approval of AstraZeneca and Daiichi Sankyo’s Enhertu as a treatment for a brand-new category of breast cancer, it quickly became clear that oncologists would need to know who should receive the drug and who shouldn’t.
And now Roche has received the first FDA approval for a companion diagnostic to identify patients carrying this HER2-low status—a more precise characterization of breast tumors that was previously more binary, relying largely on positive and negative labels.
“Previously, metastatic breast cancer patients with a lower level of HER2 expression were considered to be part of the HER2-negative population and had no HER2-targeted treatment options,” Roche Diagnostics CEO Thomas Schinecker said in a release. “Now, they may be eligible for a HER2-targeted therapy, significantly increasing the number of patients who could have improved outcomes.”
Data from a landmark clinical trial unveiled this summer showed HER2-targeting Enhertu therapy could cut the risk of disease progression or death in this new category by about 50% among people who had previously tried other treatments including chemotherapy.
The National Cancer Institute said that of the more than 287,000 new cases of breast cancer that will be diagnosed in the U.S. this year, about 80% to 85% would have been considered HER2-negative under the old definitions. Out of those, about 60% could be classified HER2-low.
Roche, meanwhile, estimates that the HER2-low group includes about half of all people with metastatic breast cancer. The pharma’s HER2-targeting therapies Herceptin and Kadcyla have previously had little to no impact on HER2-low patients, but researchers believe Enhertu may be more successful by binding to just a few cells in the tumor and also killing cells in the vicinity with its toxic payload.
AstraZeneca and Daiichi Sankyo’s phase 3 study, named Destiny-Breast04, also demonstrated Enhertu’s benefits across other patient subgroups, including in both hormone receptor-positive and negative disease.
The results were presented at the annual meeting of the American Society for Clinical Oncology in June and published in the New England Journal of Medicine. The antibody-drug conjugate’s FDA approval followed just two months later and four months ahead of schedule.
Roche’s HER2-low test was used as part of the Destiny-Breast04 study. Going forward, the company’s previously approved Pathway anti-HER2 (4B5) immunohistochemistry diagnostic will include a new scoring algorithm and a lower cutoff that helps pathologists to identify low expressors of HER2.