Abstract:Objective To explore the efficacy and safety of programmed cell death receptor 1 (PD-1) inhibitor combined with apatinib in the treatment of human epidermal growth factor receptor2 (HER2)-negative advanced gastric cancer after second-line treatment failure. Methods Clinical data of 60 HER2 negative advanced gastric cancer patients who failed second-line treatment in the Oncology Department of First Hospital of Qinhuangdao from April 2020 to April 2022 were retrospectively analyzed. According to the treatment regimen, the patients were divided into the study group (received PD-1 inhibitor combined with apatinib therapy,n =28) and the control group (received apatinib monotherapy,n =32), and were followed up for 2 years. The differences of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and incidence of adverse reactions between the two groups were analyzed. Results There was no significant difference in ORR between the study group and the control group (7.1%vs 3.1%,χ 2=0.014,P =0.906). The DCR in the study group was higher than that in the control group (67.9%vs 40.6%,χ 2=4.450,P =0.035). There was no statistically significant difference in the incidence of adverse reactions ( P ＞0.05), and no treatment-related deaths occurred in both groups. The median PFS (5.1 monthsvs 3.5 months) and medican OS (9.7 monthsvs 7.8 months) in the study group were longer than those in the control group, with statistically significant differences ( P ＜0.05). Multivariate Cox analysis suggested that the combination of apatinib and PD-1 inhibitors was an independent prognostic factor for PFS and OS ( P ＜0.05). Conclusion The combination of apatinib and PD-1 inhibitor in third-line treatment for HER2 negative advanced gastric cancer can increase DCR rate, improve PFS and OS, and the adverse reactions can be tolerabled.