Abstract
BACKGROUND: Diffuse-type gastric or gastroesophageal junctional cancers (DGC) often presents with peritoneal dissemination, leading to poor prognosis. This study assessed the efficacy of nivolumab-based therapies in patients with human epidermal growth factor receptor 2-negative DGC with peritoneal dissemination. MATERIALS AND METHODS: This retrospective analysis included patients with DGC treated between June 2017 and March 2024. One cohort (n = 185) received nivolumab monotherapy as a third- or later-line treatment; the other (n = 117) received nivolumab plus chemotherapy as a first-line treatment. RESULTS: In the monotherapy cohort, 150 (81%) of 185 patients had peritoneal dissemination, which was significantly associated with worse progression-free survival (1.6 versus 2.5 months, P = 0.03) and overall survival (OS: 4.5 versus 7.2 months, P = 0.01) compared with those without peritoneal dissemination. In the first-line cohort, 74 (63%) of 117 patients had peritoneal dissemination. No significant differences were observed in progression-free survival (6.5 versus 9.6 months, P = 0.14) and OS (15.5 and 25.0 months, P = 0.47) between patients with and without peritoneal dissemination. Patients with peritoneal dissemination exhibited poor disease control in both cohorts, but those achieving complete or partial response had longer OS. The modified Glasgow Prognostic Score significantly impacted prognostic outcomes in both cohorts, while programmed death-ligand 1 status showed no statistical significance. Adverse events were manageable, with no treatment-related deaths. CONCLUSIONS: First-line nivolumab plus chemotherapy demonstrated limited efficacy in human epidermal growth factor receptor 2-negative DGC with peritoneal dissemination but achieved a comparable OS to patients without peritoneal dissemination, supporting its potential as a first-line treatment.