Health Canada Approves HER2-Directed Therapy for Patients with HER2-Low Metastatic Breast Cancer

Health Canada recently approved Enhertu™ for treating adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.

Patients with hormone receptor-positive (HR+) breast cancer should have received at least one and be no longer considered eligible for endocrine therapy.1 

Enhertu (trastuzumab deruxtecan) is a specifically engineered HER2-directed antibody-drug conjugate (ADC) jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

The approval by Health Canada on January 6, 2023, was based on the DESTINY-Breast04 Phase III trial results.

"Since the approval of HER2-targeted therapies in breast cancer more than twenty years ago, only patients with HER2-positive disease have been eligible for these therapies – leaving those with tumors with lower levels of HER2 expression with limited effective treatment options," said Dr. Jan-Willem Henning, Medical Oncologist, Tom Baker Cancer Centre, and Clinical Associate Professor, Cumming School of Medicine, University of Calgary, in a press release on January 12, 2023.

"The recent Health Canada approval of Enhertu in the HER2-low patient population is a significant milestone in the treatment of metastatic breast cancer and is the first anti-HER2 molecule to demonstrate efficacy outside of traditional HER2-positive breast cancer.

"Based on the promising data from the DESTINY-Breast04 trial, we're now able to differentiate levels of HER2 expression to redefine how we classify and treat metastatic breast cancer, providing additional patients with the opportunity to benefit from HER2-directed therapy."

In Canada, 10% of newly diagnosed breast cancers are metastatic; for those initially diagnosed with early-stage breast cancer, approximately 30% will progress to metastatic disease.

HER2 expression is currently defined as either positive or negative and is determined by an IHC test which estimates the amount of HER2 protein on a cancer cell, and/or an ISH test, which counts the copies of the HER2 gene in cancer cells.

However, approximately half of all breast cancers are HER2-low, and previously these patients had limited effective treatment options following progression on endocrine (hormone) therapy.

Health Canada reviewed and approved Enhertu for this indication under the Priority Review and Project Orbis FDA collaboration pathways seven months from filing, enabling the timely availability to bring this new treatment option to HER2-low breast cancer patients as quickly as possible.

Note: ENHERTU is U.S. FDA-approved for treating several types of cancer.