Temporal dynamics of CLDN18.2 expression following zolbetuximab treatment in advanced gastric cancer

Background

Zolbetuximab plus chemotherapy is the standard of care for unresectable advanced gastric cancer that is human epidermal growth factor receptor 2-negative and claudin-18 isoform 2 (CLDN18.2)-positive (2+/3+ staining intensity in ≥75% of tumor cells). The dynamics of CLDN18.2 expression after zolbetuximab remain poorly understood.

Materials and methods

Using immunohistochemistry, we retrospectively assessed CLDN18.2 expression in tumor samples from CLDN18.2-positive advanced gastric cancer collected before and after zolbetuximab-containing chemotherapy. Expression levels were evaluated based on the proportion of cells with ≥2+ staining intensity using multiple cut-off values (75%, 40%, and 25%).

Results

Among 65 patients who received zolbetuximab-containing therapy, CLDN18.2 status was assessable at both baseline and disease progression in 15 patients. At disease progression, 53.3% of cases converted to CLDN18.2-negative. CLDN18.2 positivity was retained in 66.7% and 73.3% of patients when applying 40% and 25% cut-off levels, respectively.

Conclusions

CLDN18.2 expression above the ≥75% cut-off declined after zolbetuximab, but lower-level expression was often preserved, supporting the potential for subsequent targeted therapy.