Dr. Catenacci on Navigating HER2 Testing in Gastric/GEJ Cancer

Daniel Catenacci, MD, associate professor of medicine, adult gastrointestinal medical oncologist, director, Gastrointestinal Oncology Program, assistant director of translational research, Comprehensive Cancer Center, University of Chicago Medicine, discusses navigating HER2 testing in gastric and gastroesophageal (GEJ) adenocarcinoma.

All patients with gastric/GEJ adenocarcinoma should undergo circulating tumor DNA (ctDNA) testing at diagnosis, Catenacci explains. If the liquid biopsy identifies a HER2 amplification, the patient can be spared a tissue biopsy.

However, if the ctDNA test is negative for HER2 amplifications but highly positive for other genetic events, the patient’s disease should be considered HER2 negative, even if there are pockets of HER2-amplified cells, Catenacci says. This is because the predominant genetic abnormality is non-HER2, so utilizing non–HER2-directed therapies would be optimal.

In patients for whom ctDNA testing does not yield any relevant findings, a tissue biopsy is needed to determine whether their disease is driven by HER2. This is critical because the HER2-targeted agent fam-trastuzumab deruxtecan-nxki (Enhertu) is FDA approved for use in patients with locally advanced or metastatic HER2-positive gastric/GEJ adenocarcinoma who have received a previous trastuzumab (Herceptin)-based regimen.

Historically, the second-line treatment of patients with gastric/GEJ adenocarcinoma consisted of paclitaxel plus ramucirumab (Cyramza), a non–HER2-directed regimen. With the addition of trastuzumab deruxtecan to the second-line setting, repeat testing to confirm the presence or absence of HER2 amplifications is critical, Catenacci concludes.