Dr Uboha on the Role of Biomarkers for Guiding Esophageal Adenocarcinoma Treatment Selection

"Biomarkers play a critical role in treatment decisions for patients, particularly those with esophageal adenocarcinomas, including GEJ adenocarcinoma."

Nataliya Uboha, MD, PhD, an associate professor and researcher in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health, discussed the central role of biomarkers in guiding treatment selection for patients with esophageal adenocarcinoma, including those with gastroesophageal junction (GEJ) adenocarcinoma.

In the early-stage setting, all patients with esophageal or GEJ adenocarcinoma should undergo testing for microsatellite instability (MSI) and mismatch repair deficiency (dMMR), Uboha noted. Treatment pathways differ significantly for this population vs for patients with different disease features, as tumors that are MSI-high or dMMR demonstrate high sensitivity to immunotherapy, she explained. These patients should receive immune checkpoint blockade rather than chemotherapy in the neoadjuvant setting prior to surgical resection, Uboha added.

For patients with more advanced disease, biomarker testing is critical to informing a personalized treatment approach, Uboha emphasized. In adenocarcinoma, standard chemotherapy typically consists of fluorouracil, leucovorin, and oxaliplatin (FOLFOX), a regimen that is also frequently employed in esophageal squamous cell carcinoma (ESCC), she stated. However, additional agents may be incorporated depending on biomarker results, Uboha said.

Immune checkpoint inhibitors directed at PD-1, such as pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq), have demonstrated activity in both adenocarcinoma and ESCC, primarily in tumors with PD-L1 expression, Uboha explained. Therefore, PD-L1 testing remains essential to identifying candidates most likely to benefit from immunotherapy, she added.

In adenocarcinoma, further biomarker assessments are also warranted, Uboha said. HER2 remains a validated target in this setting, whereas Claudin 18.2 (CLDN18.2) has emerged as a novel biomarker, particularly in distal esophageal and GEJ adenocarcinomas, she noted. Zolbetuximab-clzb (Vyloy), an anti-CLDN18.2 monoclonal antibody, has demonstrated clinical benefit when combined with first-line chemotherapy in patients whose tumors express CLDN18.2, Uboha concluded.