Real-world adoption and sequencing of CLDN18.2, PD-L1, and HER2 testing in advanced gastric and gastroesophageal junction adenocarcinoma.

Abstract

4035 Background: The FDA approval of zolbetuximab for CLDN18.2-positive advanced gastric and gastroesophageal junction adenocarcinoma (GEA) in Oct 2024, based on the SPOTLIGHT and GLOW trials, represents an important advance in biomarker-driven therapy. We aimed to describe real-world adoption of CLDN18.2 testing in the US, and CLDN18.2 co-expression with other clinically relevant biomarkers. Methods: Using the US-based, electronic health record-derived deidentified Flatiron Health Research Database, we evaluated biomarker testing patterns among patients diagnosed after 2016 across three periods: pre-SPOTLIGHT publication (2016–2022), post-SPOTLIGHT/pre-FDA approval (Jan 2023–Sep 2024), and post-FDA approval (Oct 2024 onward). We assessed CLDN18.2 testing uptake and co-expression with PD-L1 and HER2. Results: In total, our study included 11,099 patients (7,515 pre-SPOTLIGHT, 2,364 pre-FDA, 1,220 post-FDA). Compared to HER2 testing, 1.1% had CLDN18.2 testing pre-SPOTLIGHT, 21.3% pre-FDA and 39.5% post-FDA. The prevalence of biomarker positivity was as follows: HER2 20.1% (2,617/13,033), PD-L1 25.6% (1,913/7,487), CLDN18.2 42.6% (473/1,109). Among patients tested for all three biomarkers with available result dates, 69.9% underwent upfront comprehensive testing (HER2, PD-L1, CLDN18.2 within one week), while 30.1% had sequential testing, with a median interval of 91 days between tests. Among 1,034 patients tested for all three biomarkers, 13.9% were dual PD-L1/CLDN18.2 positive, and 4.4% were triple-positive. Conclusions: In this real-world analysis, CLDN18.2 testing uptake increased following SPOTLIGHT but remained incomplete, and nearly one-third underwent sequential rather than upfront comprehensive biomarker testing, resulting in clinically meaningful delays. These findings highlight the need for improved education and implementation of upfront, comprehensive biomarker testing strategies to optimize treatment sequencing and preserve therapeutic options for patients with GEA.