Temporal dynamics of CLDN18.2 expression following zolbetuximab treatment in advanced gastric cancer
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Published on: February 9, 2017
K Yamamoto1, I Nakayama1, N Sakamoto2,3
1Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba.
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.
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