Dr. Jones on Targeting HER2 Alterations in CRC

Jeremy C. Jones, MD, hematologist and oncologist, Mayo Clinic, discusses targeting HER2 alterations in colorectal cancer (CRC).

HER2 amplification occurs in approximately 3% of patients with metastatic CRC, Jones explains. However, these alterations are not identifiable without genetic testing, Jones says. Cell-free DNA–based testing can identify copy number variance or HER2-amplification status; however, immunohistochemistry testing with reflex fluorescence in situ hybridization is the most effective way to test for HER2 positivity, Jones says.

A number of clinical trials evaluating HER2 positivity in CRC led to drug development for this patient subgroup, Jones explains. Most trials studied therapeutic options for patients with HER2-positive breast cancer, Jones adds. For example, the ongoing phase 2 DESTINY-CRC02 trial (NCT04744831) is evaluating the efficacy of the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-overexpressing locally advanced, unresectable, or metastatic CRC.

Previous findings from the phase 2 DESTINY-CRC01 trial (NCT03384940) reported a confirmed overall response rate of 45.3% with trastuzumab deruxtecan in patients with HER2-overexpressing metastatic CRC. The median progression-free survival was 6.9 months, and the disease control rate was 83%, concludes Jones.