FDA Approves Diagnostic Test to Identify Patients with Metastatic Breast Cancer Expressing Low Levels of HER2 Protein

The FDA approved the only companion diagnostic that is indicated to assess low levels of HER2 proteins in patients with metastatic breast cancer.

The FDA has approved the 4B5 Rabbit Monoclonal Primary Antibody (Roche; Pathway anti-HER2/neu) to identify patients with metastatic breast cancer (mBC) who may be eligible for target treatment fam-trastuzumab deruxtecan-nxki (Enhertu; AstraZeneca, Daiichi Sankyo). The treatment will also be commercialized by AstraZeneca and Daiichi Sankyo.

The 4B5 test is engineered to be a human epidermal growth factor receptor 2 (HER2)-directed antibody drug conjugate (ADC). Patients who would qualify to take fam-trastuzumab deruxtecan-nxki must have low expression of HER2.

“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. Now, they may be eligible for a HER2-targeted therapy, significantly increasing the number of patients who could have improved outcomes,” said Thomas Schinecker, CEO of Roche Diagnostics, in a press release.

The receptor protein HER2 propels fast cancer growth. Patients who have tumors that express high levels of HER2 are considered HER2-positive—these patients are eligible to receive HER2-targeted treatment. If low levels of the HER2 protein are found in the tissue sample, the patient is classified as HER2-negative, and nearly half of all patients with mBC express low levels of HER2.

The 4B5 Rabbit Monoclonal Primary Antibody test can be used to standardize immuno-histochemistry (IHC) processes and decrease human error in the laboratory setting. It includes an algorithm that allows pathologists to score HER2 expression and identify the low expressors.

AstraZeneca and Daiichi Sankyo sponsored the DESTINY-Breast04 trial to evaluate the efficacy of the 4B5 test in identifying patients with mBC who had tumors that expressed low levels of the HER2 protein. This trial then evaluated treatment of low expressor patients using fam-trastuzumab deruxtecan-nxki.

The results of the trial found a 50% decrease in risk of mBC recurrence or death among those whose tumors express low levels of HER2 protein and were treated with fam-trastuzumab deruxtecan-nxki. This treatment was also observed to increase gains by 6 months compared to the standard of care.

In December 2019, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (for adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting.)

In May 2022, the FDA granted regular approval with an updated indication for adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy.

Breast cancer is the most diagnosed cancer in the world. Researchers estimate that more than a half-million people die from the disease every year, and almost 4 times as many individuals are diagnosed with it.

“Roche is proud to lead the way in HER2 diagnostics through critical innovations that support the identification of patients who may benefit from novel HER2-targeted therapies,” Schinecker concluded in the press release.

Reference

Roche Diagnostics. Roche receives FDA approval for first companion diagnostic to identify patients with HER2 low metastatic breast cancer eligible for Enhertu. October 4, 2022. Accessed on October 4, 2022. Roche website. https://diagnostics.roche.com/global/en/news-listing/2022/roche-receives-fda-approval-for-first-companion-diagnostic-to-id.html