Development and validation of the gastric risk immuno-progression score (GRIPS) in advanced gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy plus nivolumab: Results from the ORACLE study.

4062 Background: The addition of nivolumab to chemotherapy is approved for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma with PD-L1 CPS ≥5. Identifying predictive tools for disease progression in this setting remains a clinical need. This study introduces the Gastric Risk Immuno-Progression Score (GRIPS), a novel score derived from variables associated with progression-free survival (PFS) in a real-world cohort. Methods: We conducted a multicenter retrospective study on 90 patients with gastric/GEJ adenocarcinoma treated with first-line chemotherapy plus nivolumab between 2022 and 2024. The GRIPScore was constructed using five dichotomous variables associated with unfavorable PFS in univariate analysis: Neutrophil-to-Lymphocyte Ratio (NLR > 2.68), ECOG Performance Status (≥2), Smoking status (never smoker), CA19.9 at diagnosis (UNL) and primary tumor resection (no resection). Each variable was scored as 1 (prognostically negative) or 0 (prognostically positive), and a total score (0–5) was calculated. Patients were categorized into low-risk (GRIPS 0–2) and high-risk (GRIPS 3–5) groups. PFS and OS were analyzed using Kaplan-Meier methods. Hazard Ratios (HRs) were calculated, and the discriminatory ability of the GRIPS was evaluated using Harrell's C-index. Results: The median PFS for the entire cohort was 11.55 months (95% CI: 7.60–13.26). Stratifying patients by GRIPS revealed a marked difference in outcomes between the low-risk and high-risk groups. Low-risk patients (GRIPS 0–2) had a median PFS of 13.16 months (95% CI: 9.01–18.91), while high-risk patients (GRIPS 3–5) had 4.11 months (95% CI: 2.37–11.77). This difference was significant (log-rank test, p = 0.0023; HR: 3.55, 95% CI: 1.58–8.02). Similarly, low-risk patients had a median OS of 21.25 months (95% CI: 13.77–21.25) compared to 11.90 months (95% CI: 4.03–16.10) for high-risk patients (log-rank test, p = 0.0313; HR: 2.73, 95% CI: 1.09–6.81). Harrell’s C-index for PFS was 0.648 (95% CI: 0.552–0.743), indicating moderate discriminatory ability. Conclusions: The GRIPS effectively stratifies patients with advanced gastric and gastroesophageal junction adenocarcinoma treated with a combination of chemotherapy + nivolumab into distinct risk groups for PFS and OS. High-risk patients experience significantly shorter survival, highlighting the potential clinical utility of GRIPS for personalized treatment strategies. Further prospective validation is warranted to refine its application in clinical practice. GRIPScore N° of patients (%) mOS (m) mPFS (m) Low-risk (0-2) 51 (45.9) 21.25 (95% CI: 13.77–21.25) 13.16 (95% CI: 9.01–18.91) High-risk (3-5) 21 (18.9) 11.90 (95% CI: 4.03–16.10) 4.11 (95% CI: 2.37–11.77) Not evaluable 18 (16.2)