ArticleAmerican journal of cancer research2025
Comparison of Alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: an analysis stratified by HER2 status.
Article in American journal of cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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- Comparison of Alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: an analysis stratified by HER2 status.American journal of cancer research · 2025Article
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10 authors.
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Abstract
backgroundImmunotherapy-based regimens are standard first-line treatment for advanced gastroesophageal junction or gastric cancer (GEJ/GC), but their efficacy in alpha-fetoprotein-producing gastric cancer (AFPGC) remains unclear. We investigated the positivity of AFP influenced immunotherapy outcomes in advanced GEJ/GC, and examined whether this role is influenced by the patient's HER2 status. Secondly, we aim to assess the efficacy of anti-angiogenic agents within advanced AFP-positive GEJ/GC (AFP-GEJ/GC).
methodsThis retrospective study analyzed patients with advanced GEJ/GC receiving first-line immunotherapy, stratified by HER2 status. AFP-positive GEJ/GC was defined as a pretreatment serum AFP level ≥ 20 ng/mL or positive immunohistochemistry.
resultsIn the overall population, the AFP-GEJ/GC group (n = 79) showed similar median progression-free survival (mPFS; 7.30 vs. 8.53 months; P = 0.42) and median overall survival (mOS; 21.80 vs. 19.70 months; P = 0.38) compared with the AFP-negative group (n = 478). In the HER2-negative cohort, 246 patients receiving standard two-drug chemotherapy combined with PD-1 inhibitors, the AFP-GEJ/GC group (n = 16) exhibited shorter mPFS (5.40 vs. 7.0 months; P = 0.02) and numerically worse mOS (11.40 vs. 16.80 months; P = 0.24) compared with the AFP-negative group (n = 230), despite similar objective response rates (ORRs 50.0% vs. 45.2%; P = 0.80) and disease control rates (DCRs 93.8% vs. 90.4%; P > 0.99). In the HER2-positive cohort, 107 patients receiving standard chemotherapy-based regimens, AFP-GEJ/GC (n = 14) showed numerically shorter mPFS (7.67 vs. 12.20 months; P = 0.60) but similar mOS (32.40 vs. 28.30 months; P = 0.38) versus AFP-negative group (n = 93). Notably, anti-angiogenic combination therapy did not statistically improve mPFS and mOS in AFP-GEJ/GC (n = 79). However, in the HER2-negative AFP-GEJ/GC group (n = 47), anti-angiogenic combination therapy (n = 31) was associated with a modestly longer mPFS (6.33 vs. 5.40 months; P = 0.02) and a numerical improved mOS (15.70 vs. 11.40 months; P = 0.15) compared with chemo-immunotherapy (n = 16).
conclusionAFP positivity may indicate inferior efficacy of first-line chemo-immunotherapy in HER2-negative advanced GEJ/GC, and anti-angiogenic therapy warrants further evaluation as a potential strategy to improve outcomes.
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