CLDN18.2 IHC cutoff and efficacy of anti-CLDN18.2 therapy in gastric and gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis.

441 Background: Assay platforms and immunohistochemistry (IHC) cutoffs for CLDN18.2 positivity vary across trials of anti-CLDN18.2 therapy. Whether higher cutoffs are associated with greater treatment effect remains uncertain and has implications for patient selection. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through September 4, 2025, for first-line, HER2-negative advanced/metastatic gastric or gastroesophageal junction adenocarcinoma trials testing anti-CLDN18.2 therapy plus chemotherapy and reporting hazard ratios (HRs) for PFS and/or OS. The risk of bias for randomized trials was assessed using RoB 2. We pooled log-HRs using random-effects models and summarized the results from single-arm cohorts qualitatively. Prespecified exploratory moderators were IHC cutoff (%) and assay platform (e.g., VENTANA RxDx vs CLAUDETECT18.2). Primary endpoints were PFS and OS expressed as hazard ratios; random-effects (DerSimonian-Laird) models pooled log-HRs, heterogeneity was assessed (tau^2 and I^2), small-study bias was not evaluated given k