Neoadjuvant PD-1 inhibitor plus apatinib and chemotherapy versus apatinib plus chemotherapy versus chemotherapy alone in patients with locally advanced gastric cancer.

Programed cell death protein-1 (PD-1) inhibitor, apatinib, and chemotherapy show synergistic antitumor effect in gastric cancer. This study aimed to evaluate this combination as a neoadjuvant therapy in locally advanced gastric cancer (LAGC). In this retrospective study, data from 179 LAGC patients who underwent neoadjuvant therapy with a PD-1 inhibitor plus apatinib and chemotherapy (PAC group, n=56), apatinib and chemotherapy (AC group, n=50), or chemotherapy alone (C group, n=73) were analyzed. The PAC group displayed a numerically higher radiologic objective response rate than the AC group (73.2% vs. 60.0%, P=0.149) and significantly higher than the C group (73.2% vs. 35.6%, P<0.001). Tumor resection rates between the PAC and AC groups were not significantly different (100.0% vs. 94.0%, P=0.102) but were higher in the PAC group compared to the C group (100.0% vs. 89.0%, P=0.010). Pathological evaluations revealed comparable R0 resection rates across all groups (P=0.873) and a non-significantly higher pathological complete response rate in the PAC group compared to the AC group (26.8% vs. 17.0%, P=0.236), while significantly higher than the C group (26.8% vs. 7.7%, P=0.005). Moreover, the PAC group exhibited a longer progression-free survival compared to the AC (P=0.036) and C (P<0.001) groups, an extended disease-free survival compared to the C group (P=0.002), and improved overall survival compared to the AC (P=0.028) and C (P=0.002) groups. Adverse events were generally comparable, with the highest incidence of peripheral neuropathy observed in the PAC group (26.8%, P=0.020). PD-1 inhibitor plus apatinib and chemotherapy may represent an effective neoadjuvant regimen for LAGC management, necessitating further validation.