AbstractBackgroundWhile the efficacy of immune checkpoint inhibitors (ICIs) reportedly varies among metastatic sites and progression patterns (classified as systemic progression [SP] or mixed progression [MP]), the clinical efficacy of ICIs against gastric cancer remains unclear. The response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer was investigated retrospectively.MethodsSeventy‐four advanced gastric cancer patients with measurable lesions who received nivolumab monotherapy between 2015 and 2020 were enrolled. Progression‐free survival (PFS), overall survival, response at each metastatic site, and clinical outcomes according to progression pattern were analyzed retrospectively. SP and MP were defined as progression in more than half of the lesions and progression in half or fewer of the lesions, respectively, in cases evaluated as progressive disease.ResultsThirty‐five (47%) and 27 (36%) patients had SP and MP, respectively, and 12 (16%) patients experienced no progression. The progression rates of target lesions in the lung (44%) and liver (57%) were significantly higher than that in the lymph nodes (18%) (lung vs. lymph node,p< 0.001; liver vs. lymph node,p= 0.03). Patients with MP had superior PFS to those with SP (median, 2.6 vs. 1.5 months; HR, 0.42; 95% CI, 0.23–0.76;p= 0.004). In MP group, patients with treatment beyond progression (TBP) with nivolumab had a trend of longer post‐progression survival than those without TBP (median, 8.0 vs. 4.0 months; HR, 0.55; 95% CI, 0.23–1.29;p= 0.161).ConclusionPatients with MP had a longer PFS than those with SP. Lung and liver metastases had a poorer response to an ICI than lymph node metastases.