Real-world efficacy of first-line chemotherapy plus nivolumab in gastric and GEJ adenocarcinoma patients: The ORACLE study.

e16087 Background: Nivolumab (NIV) plus chemotherapy (CHT) is the standard first-line treatment for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma with PD-L1 combined positive score (CPS) ≥ 5, based on phase 3 trials. Real-world data are essential to validate these results. Methods: We conducted a multicenter retrospective study (2022-2024) on 90 patients (pts) with PD-L1 CPS ≥ 5 gastric/GEJ adenocarcinoma treated with first-line CHT plus NIV. Clinical pathological features are described in Table 1. Endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). We assessed treatment response using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria: complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Results: At a median follow-up of 7 months (m), median OS was 14.6 m (95%CI: 11.9–21.24), and median PFS was 11.78 m (95%CI: 7.6–15.6). ORR was 46.7%, and DCR was 76.7%. Responders (CR/PR) had better outcomes than non-responders (SD/PD): median PFS of 15.6 m (95%CI: 11.5–25.5) vs. 4.3 m (95% CI: 3.2–9) (p < 0.0001) and median OS not reached vs. 10.2 m (95%CI: 6.8–13.9) (p < 0.0001). Early progressors (PD within 3–6 m) had worse outcomes, with median OS of 5.5 m (95%CI: 3.9–10.2) and median PFS of 2.3 m (95%CI: 1.9–3) vs. OS of 21.2 m (95%CI: 13.8–21.2) and PFS of 15.6 m (95% CI: 11.5–19) in other pts (p < 0.0001). Immune-related toxicity occurred in 21 pts (23.3%), leading to treatment discontinuation in 6 cases (7.1%). Conclusions: This real-world study confirmed the efficacy and safety of NIV plus CHT in advanced gastric/GEJ adenocarcinoma with PD-L1 CPS ≥ 5. Response to treatment emerged as a key prognostic factor for survival. Further follow-up is needed to validate these findings and identify predictive factors for response and progression. Clinicopathologic features. Clinicopathologic features N=90(%) Age>50≤50 78 (86.7)12 (13.3) GenderMF 58 (64.4)32 (35.6) ECOG PS0-1≥2 84 (93.3)6 (6.7) Primary tumor locationstomachcardia/GEJ 48 (53.3)42 (46.7) Primary tumor resectionYN 32 (35.5)58 (64.4) Histology Type IntestinalDiffuse signet ring cellsNot Assessed 23 (25.5)35 (38.8)19 (21.1)32 (35.5) MMR/MSI status pMMR/MSSdMMR/MSI-HNot Assessed 76 (84.4)10 (11.1)4 (4.5) PD-L1 CPS5≤CPS<10≥10 27 (30)57 (63.3) Metastasis Siteslivernodeslungperitoneumother 24 (26.7)38 (42.2)5 (5.5)24 (26.7)9 (10) Chemotherapy regimenFOLFOXXELOX5FU 81 (90)5 (5.5)4 (4.5)