Abstract 4587: Retrospective analysis of claudin-18.2 expression in ethnically diverse patients with gastroesophageal adenocarcinoma
Authors: Sara Wallam, Jimyung Park, Ryan H. Moy
Journal: Cancer Research (2025)

Abstract Background: Claudin-18.2 (CLDN18.2), a tight junction molecule, is a novel therapeutic target for patients with advanced gastroesophageal adenocarcinoma. Recent phase III trials demonstrated improved survival with the addition of an anti-CLDN18.2 antibody (zolbetuximab) to first-line chemotherapy. However, expression of CLDN18.2 and its association with other biomarkers, especially in racial and ethnic minorities, remains poorly defined. We evaluated CLDN18.2 expression, its association with demographic and clinicopathologic characteristics, and its prognostic potential in a small cohort of ethnically diverse patients. Methods: We conducted a single-center retrospective cohort study among patients with gastroesophageal adenocarcinoma in whom CLDN18.2 immunohistochemistry had been performed. Positivity was defined as moderate-to-strong expression in ≥75% of tumor cells. We extracted demographic and clinicopathologic data from the electronic medical record. Associations with CLDN18.2 were investigated using the t-test and chi-square test. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. P-value &amp;lt;0.05 was considered statistically significant. Results: Among 75 evaluable patients, 42.7% were CLDN18.2 positive. Mean age was 66.2 years (SD, 13.2 years), 34.7% were female, and 62.7%, 18.7%, and 18.7%, had primary gastric, gastroesophageal junction, and esophageal tumors, respectively. At diagnosis, 32% were metastatic. The cohort was 49.3% White, 12% Black, 8% Asian, and 30.7% Other/Unknown, and 20% identified as Hispanic. By ethnicity, 53.3% of Hispanic patients were CLDN18.2 positive compared to 38.2% of non-Hispanic patients. By race, 37.8% of White, 44.4% of Black, and 50% of Asian patients were CLDN18.2 positive. In univariate analyses, CLDN18.2 positivity was significantly associated with female sex (p=0.002) and HER2 negativity (p=0.040). TP53 mutations were found in 65.2% of patients with available next generation sequencing data, but there was no association with CLDN18.2. CLDN18.2 was also not associated with response to neoadjuvant therapy in non-metastatic patients, progression-free survival in metastatic patients, or overall survival in the total population. Conclusions: This study provides new information on CLDN18.2 expression in an ethnically diverse population and suggests that Hispanic patients may have higher rates of CLDN18.2 positivity than non-Hispanic patients. However, this finding lacks statistical significance, likely due to the small sample size. We also demonstrate the association between CLDN18.2 and female sex and lack of association with survival, consistent with published data. Future research should further investigate differences in CLDN18.2 expression and identify subpopulations of patients who may benefit from CLDN18.2 targeted therapies. Citation Format: Sara Wallam, Jimyung Park, Ryan H. Moy. Retrospective analysis of claudin-18.2 expression in ethnically diverse patients with gastroesophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4587.