Association between the presence of malignant ascites and survival outcomes of gastric cancer patients treated with nivolumab plus chemotherapy.

e16057 Background: Malignant ascites is associated with poor outcomes in advanced gastric cancer, but its prognostic value has not been confirmed in the context of 1 st line immune checkpoint inhibitor (ICI)-based chemotherapy. This study aimed to investigate the prognostic significance of ascites in patients receiving nivolumab plus chemotherapy, and to evaluate whether malignant ascites impacts the survival benefit of nivolumab plus chemotherapy compared to chemotherapy alone. Methods: This single-center study included patients with advanced gastric cancer treated with first-line nivolumab plus chemotherapy (n = 322) or chemotherapy alone (n = 385) between June 2021 and August 2024. Peritoneal involvement and grading of ascites were assessed using computed tomography imaging. Patients were classified into three groups: no peritoneal metastases (PM), PM without ascites, and PM with ascites. Progression-free survival (PFS) and overall survival (OS) were analyzed across these groups. Results: Among patients treated with nivolumab plus chemotherapy, those in the PM with ascites group showed significantly worse outcomes (median PFS 5.23 months) compared to those in the no PM (median PFS 11.05 months) and PM without ascites groups (median PFS 11.08 months) (P < 0.001). A similar trend was observed in OS (no PM: median 22.3 months, PM without ascites: median 22.4 months, PM with ascites: median 12.5 months (P < 0.001). Whereas nivolumab plus chemotherapy was associated with favorable survival outcomes for patients in the no PM or PM without ascites groups as compared to chemotherapy alone (median PFS: 11.05 vs 6.48 months; HR 0.63, 95% CI 0.49–0.81; and median OS: 22.3 vs 15.8 months; HR 0.69, 95% CI 0.52–0.92), such survival benefits were not observed in the PM with ascites group (median PFS: 5.23 vs 4.80 months; HR 0.83, 95% CI 0.64–1.09, P = 0.19; and median OS: 12.5 vs 11.6 months; HR 0.94, 95% CI 0.70–1.27, P = 0.7). The survival benefit with the addition of nivolumab among patients with malignant ascites was not evident for subgroups with PD-L1 CPS ≥5 (PFS: HR 0.64, 95% CI 0.35–1.17, P = 0.147; OS: HR 0.99, 95% CI 0.48–2.06, P = 0.978) and deficient mismatch repair tumors (PFS: HR 0.40, 95% CI 0.11–1.42; OS: HR 1.23, 95% CI 0.30–4.98, P = 0.776). Conclusions: The presence of ascites was associated with poor survival outcomes with nivolumab plus chemotherapy and minimal benefit from the addition of nivolumab to chemotherapy in patients with gastric cancer. Our findings indicate that malignant ascites may be considered a stratification factor in future clinical trials, and underscore the need to develop novel therapeutic approaches to improve survival outcomes for patients with malignant ascites.