Prior immunotherapy enhances survival outcomes of third‐line apatinib treatment in advanced gastric cancer: A retrospective cohort study

The impact of prior immune checkpoint inhibitor (ICI) therapy on subsequent antiangiogenic treatment efficacy in advanced gastric cancer remains unclear. We retrospectively analyzed 134 patients with advanced gastric cancer who received apatinib as third-line treatment between January 2018 and October 2023, comparing outcomes between those with (n = 66) and without (n = 68) prior ICI exposure. The ICI-pretreated group demonstrated significantly improved survival outcomes, with longer median progression-free survival (7.1 vs. 4.2 months; HR = 0.42, 95% CI: 0.24-0.75, p = .003) and overall survival (9.0 vs. 5.1 months; HR = 0.53, 95% CI: 0.31-0.91, p = .023) compared to the ICI-naive group. Disease control rate was also higher in ICI-pretreated patients (72.7% vs. 61.8%). Subgroup analyses revealed particularly pronounced survival benefits among male patients (HR = 0.30, 95% CI: 0.14-0.65), HER2-negative patients (HR = 0.35, 95% CI: 0.18-0.69), and those with liver metastases (HR = 0.33, 95% CI: 0.15-0.76, p = .009). Prior ICI therapy emerged as an independent favorable prognostic factor for survival in multivariate analysis. These findings suggest that prior ICI therapy may enhance the efficacy of subsequent third-line apatinib treatment in patients with advanced gastric cancer, providing important insights for optimizing treatment sequencing strategies in this setting.