Impact of Pharmacogenetic Markers on the Efficacy of Neoadjuvant FLOT Chemotherapy in Patients with Gastric and Gastroesophageal Junction Adenocarcinoma.

Despite the adoption of neoadjuvant FLOT chemotherapy as standard treatment for locally advanced gastric and gastroesophageal junction cancer, many patients fail to achieve meaningful pathological response, limiting efficacy. The aim of this study was to evaluate the impact of pharmacogenetic markers on pathological response in Russian patients receiving neoadjuvant FLOT. Thirty patients with locally advanced gastric or gastroesophageal junction adenocarcinoma received neoadjuvant FLOT followed by surgery. Polymorphisms in CYP3A5 (rs776746), CYP2C8 (rs10509681, rs11572080, rs1058930), ERCC1 (rs11615), and GSTP1 (rs1695) were analyzed. Favorable pathological response (TRG0-2) was observed in 23.3% of patients, including 3.3% complete responses. Most patients (76.7%) had minimal or no regression (TRG3-5). Clinical variables were not associated with response. ERCC1 (rs11615) showed a significant association: patients with the Wt/Wt genotype had higher odds of achieving TRG0-2 (OR = 8.889; p = 0.033; 95% CI: 1.294-61.058). No associations were found for CYP3A5, CYP2C8, or GSTP1. Median PFS was 18.21 months in TRG3-5, while not reached in TRG0-2 (p = 0.108). No significant PFS differences by ERCC1 genotype were observed (p = 0.525). ERCC1 (rs11615) may serve as a potential pharmacogenetic marker of response to FLOT, supporting further research in personalized treatment strategies.