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IDDF2025-ABS-0387 Comparison of alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: clinicopathologic features and treatment outcomes analysis
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IDDF2025-ABS-0387 Comparison of alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: clinicopathologic features and treatment outcomes analysis
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Journal Article
IDDF2025-ABS-0387 Comparison of alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: clinicopathologic features and treatment outcomes analysis
2025
Overview
BackgroundImmunotherapy-based regimens are now the standard first-line treatment for advanced gastric cancer; however, it remains unclear whether patients with alpha-fetoprotein-producing gastric cancer (AFPGC) benefit from this approach. In this study, we aimed to evaluate the predictive and prognostic value of serum AFP in patients with gastric cancer receiving first-line immunotherapy and to explore whether adding anti-angiogenic agents improves outcomes in AFPGC.MethodsClinicopathological data from patients with advanced gastroesophageal junction/gastric cancer (GEJ/GC) treated with first-line immunotherapy were analyzed retrospectively. Patients were stratified into HER2-negative and HER2-positive subgroups. AFP-positive GEJ/GC (AFP-GEJ/GC) was defined as serum AFP≥20 ng/ml or immunohistochemical positivity pretreatment.ResultsIn the HER2-negative cohort (n=246), the AFP-GEJ/GC group (n=16) had significantly shorter median PFS (mPFS, 5.4 vs. 7.0 months; p=0.02) and numerically shorter median OS (mOS, 11.4 vs. 16.8 months; p=0.24) compared with the AFP-negative group, despite similar ORR (50.0% vs. 45.2%; p=0.798) and the DCR (93.8% vs. 90.4%; p > 0.999). In the HER2-positive cohort (n=155), patients with AFP-GEJ/GC (n=133) showed numerically shorter mPFS (7.67 vs. 14.07 months; p = 0.26) and similar mOS (29.0 vs. 26.1 months; p = 0.36) compared with the AFP-negative group (n=22). Among HER2-negative AFP-GEJ/GC (n=47), patients receiving anti-angiogenic combination therapy (n=31) had longer mPFS (6.33 vs. 5.40 months; p=0.02) and mOS (15.7 vs. 11.4 months; p=0.15) than those receiving standard chemoimmunotherapy (n=16).ConclusionsElevated serum AFP may predict poorer efficacy and prognosis in patients with advanced GEJ/GC treated with immunotherapy, particularly in HER2-negative subgroups. Combining anti-angiogenic agents with first-line immunotherapy could improve treatment efficacy and survival in HER2-negative AFP-GEJ/GC.
Publisher
BMJ Publishing Group LTD
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