Association of Cachexia-Related Status With Treatment Outcomes in Advanced Gastric Cancer Receiving First-Line Therapy With or Without Nivolumab

PURPOSE: The clinical significance of longitudinal cachexia-related status during first-line therapy for advanced gastric cancer remains unclear in the era of nivolumab-containing chemotherapy. We evaluated its association with outcomes according to nivolumab use. METHODS: We retrospectively analyzed 121 patients with HER2-negative unresectable advanced or recurrent gastric cancer who received first-line oxaliplatin- plus fluoropyrimidine-based chemotherapy between 2017 and 2024. Modified Glasgow Prognostic Score (mGPS) 2 status and modified European Palliative Care Research Collaborative (EPCRC)-defined cachexia status were assessed as time-dependent covariates. Progression-free survival (PFS) and overall survival (OS) were analyzed using time-dependent Cox proportional hazards models. RESULTS: The cohort included 69 patients in the non-nivolumab group and 52 in the nivolumab-containing group. Median age was 71 years, 76 patients (63%) were male, and baseline mGPS 2 was present in 37 patients (31%). The cumulative proportion of patients who met the mGPS 2 criterion by 6 months was 55% in the non-nivolumab group and 57% in the nivolumab-containing group. Time-dependent mGPS 2 status was not significantly associated with PFS (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.69-3.20; P = 0.30), but was associated with shorter OS (HR, 2.17; 95% CI, 1.15-4.10; P = 0.017). No statistically significant interaction between time-dependent mGPS 2 status and nivolumab use was observed for PFS or OS. Time-dependent modified EPCRC-defined cachexia status was not significantly associated with PFS or OS. CONCLUSIONS: Time-dependent mGPS 2 status during first-line therapy was associated with shorter OS, but not PFS.