Semiquantitative CLDN18 expression and clinical outcomes in patients with CLDN18-positive gastric cancer treated with zolbetuximab plus chemotherapy

Background: Zolbetuximab plus chemotherapy improves survival in patients with human epidermal growth factor receptor 2 (HER2)-negative, claudin 18 (CLDN18)-positive advanced gastric cancer (AGC), which is defined as ≥75% of tumor cells with moderate-to-strong membranous staining. Whether semiquantitative expression within this range influences treatment outcomes is unknown. Patients and methods: This single-center retrospective study evaluated patients with AGC treated with zolbetuximab plus chemotherapy between July 2024 and September 2025. Tumors were independently reviewed by three pathologists and categorized as having moderate (75%-94%) or high (95%-100%) CLDN18 expression. Survival, response, and safety were compared across expression levels. Results: Fifty-one patients were included in the study. Baseline characteristics were similar across the groups. The median progression-free survival was 6.7 months in both expression groups, and the median overall survival was not reached. The objective response rates were 62.5% and 71.4%, and the disease control rates were 87.5% and 85.7% in the moderate and high expression groups, respectively. The depth of response (-33.6% versus -45.8%) and early tumor shrinkage (43.8% versus 71.4%) differed modestly. The profile of treatment-related adverse events was similar across the expression groups. Specimen type (biopsy or surgical resection) had no apparent impact on treatment outcomes. Conclusions: Within the approved CLDN18-positive threshold, the semiquantitative staining proportion showed no detectable differences in the efficacy or safety of zolbetuximab plus chemotherapy.