Jeremy C. Jones, MD, discusses targeting HER2 alterations in colorectal cancer.
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.