Reduced Peripheral Blood Natural Killer Cell Proportion Predicts Poor Overall Survival in Advanced Gastric Cancer Patients Treated With Apatinib

Abstract

Background: Angiogenesis inhibition represents a key therapeutic strategy in oncology, with apatinib showing significant efficacy for advanced gastric cancer (AGC) therapy. Currently, no biomarkers can reliably predict which AGC patients will benefit most from apatinib. The purpose of this study was to evaluate apatinib plus tegafur gimeracil oteracil potassium capsule (S-1) as a second-line therapy in AGC and to investigate prognostic biomarkers associated with outcomes.

Methods: All 60 patients received apatinib (250 or 500 mg once daily) in combination with S-1 (40 mg/m², administered twice daily from day 1 to day 14). Treatment was administered in 28-day cycles, with each course encompassing two such cycles. Multiparameter flow cytometry was used to analyze the subset distribution and immunophenotypes of T cells and natural killer (NK) cells in peripheral blood mononuclear cell samples from AGC patients.

Results: Among all 60 evaluable patients, no complete responses were observed. Partial responses were observed in 33.3% (20/60) of patients (95% confidence interval (CI): 21.1-45.6%), stable disease was observed in 38.3% (23/60) of patients (95% CI: 25.7-51.0%), while progressive disease occurred in 28.3% (95% CI: 16.6-40.1%). Notably, patients with NK cell proportions greater than 17% experienced longer progression-free survival (PFS) and overall survival (OS) than those with lower proportions.

Conclusions: Apatinib combined with S-1 exhibited favorable tolerability and promising clinical activity as a second-line option for AGC patients. Importantly, we identified peripheral blood NK cell proportion as a potential predictor of treatment response, where a low NK cell proportion correlated with poorer outcomes.