This article offers an evidence-informed opinion on considerations when selecting between these first-line treatments for G/GEJ adenocarcinoma in patients with HER2-negative disease that expresses CLDN18.2 and/or PD-L1, including the reliability of biomarker scoring and interpretation, overall survival (OS) rates, toxicity profiles, and logistical practicalities. The gene discussed is ERBB2; the disease is adenocarcinoma.