Apatinib Plus PD-1 Blockade versus Chemotherapy After Prior Immunotherapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Retrospective Cohort Study.

Abstract

Objective: To compare clinical outcomes and safety of apatinib plus programmed death-1 (PD-1) blockade versus single-agent chemotherapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma previously exposed to immune checkpoint inhibitors (ICIs).

Methods: This single-center retrospective cohort included 117 adults with HER2-negative advanced G/GEJ adenocarcinoma treated after discontinuation of an ICI-containing regimen. 59 patients received apatinib plus PD-1 blockade (AP group) and 58 received single-agent chemotherapy (CT group). The primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and treatment-related adverse events (TRAEs). Survival was analyzed using Kaplan-Meier methods and Cox regression, stabilized inverse probability of treatment weighting (IPTW) and prespecified sensitivity analyses were used to assess robustness to measured confounding.

Results: ORR was numerically higher in the AP group than in the CT group (20.3% vs 8.6%, P=0.072). The DCR was significantly higher in AP group (71.2% vs 36.2%, P<0.001). Among the responders, median DoR was 5.2 months in the AP group and 2.6 months in the CT group (P<0.001). Median PFS was 4.5 months in AP group and 2.8 months in CT group (HR=0.58, 95% CI: 0.39-0.88, P=0.008). Median OS was 11.3 and 6.4 months, respectively (HR=0.55, 95% CI: 0.36-0.83, P=0.004). Multivariable Cox and stabilized IPTW analyses yielded directionally consistent survival associations (IPTW: OS HR=0.53, 95% CI: 0.36-0.79; PFS HR=0.57, 95% CI: 0.39-0.85). Any-grade TRAEs occurred in 86.4% and 91.4% of patients in AP and CT group, respectively. Grade ≥3 TRAEs occurred in 39.0% and 55.2%, respectively.

Conclusion: Apatinib plus PD-1 blockade was associated with longer survival and greater disease control than single-agent chemotherapy. Given the single-center retrospective design, limited sample size, treatment heterogeneity, incomplete biomarker characterization, and potential residual confounding, these findings are hypothesis-generating, do not establish causality, and require prospective validation.