The Efficacy And Safety Of Neoadjuvant PD-1 Blockade Plus Chemotherapy Versus Chemotherapy Alone In Locally Advanced Gastric Cancer

Objective Gastric cancer is one of the most common and serious malignant tumors of digestive system.Early-stage gastric cancer can be resected by endoscopic and surgical treatment,and the prognosis is relatively good.While most of the patients have reached advanced stage at the time of diagnosis,and the prognosis is poor.After perioperative radiotherapy and chemotherapy,the success rate of surgical operations may be improved in the patients with locally advanced gastric cancer,while the long-term prognosis is still unsatisfactory.The application of PD-1inhibitors has shown satisfying efficacy and tolerable safety in the first-line treatment of advanced gastric cancer and neoadjuvant treatment of non-small cell lung cancer.However,the efficacy and safety of neoadjuvant immunotherapy based on PD-1inhibitor in locally advanced gastric cancer remain dubious.The purpose of this study was to retrospectively investigate the efficacy and safety of neoadjuvant PD-1inhibitors plus chemotherapy versus neoadjuvant chemotherapy alone in patients with locally advanced gastric cancer,and to explore the factors that were more likely to achieve pathological complete response（p CR）in patients with locally advanced gastric cancer.Methods We performed a retrospective review of patients with locally advanced gastric cancer who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from January 1^st,2019 to December 31^st,2021.The primary aim was to investigate the differences in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy group and neoadjuvant chemotherapy group.Multivariable models for p CR were built to investigate the factors that facilitated p CR.Results1.A total of 77 patients were included in the analysis,among whom 34（44.2%）received neoadjuvant PD-1 blockade plus chemotherapy,and 43（55.8%）received neoadjuvant chemotherapy.2.A higher p CR rate was observed in the neoadjuvant PD-1 blockade plus chemotherapy group（8 of 34,23.5%vs.2 of 43,4.7%,P=0.019）.3.Multivariate logistic regression analysis of p CR revealed neoadjuvant PD-1blockade plus chemotherapy regimen promoted p CR（OR 12.95,P=0.016）.4.Regarding safety,76.5%（26 of 34）of patients in the PD-1 blockade plus chemotherapy group and 76.7%（33 of 43）of patients in the chemotherapy group experienced treatment-related adverse events,and grade 3 or worse adverse events were 29.4%（10 of 34）and 34.9%（15 of 43）,respectively.There were no neoadjuvant treatment-related deaths or delay of surgery.5.In the patients with positive PD-L1 expressions,the recurrence-free probability was higher in neoadjuvant PD-1 blockade plus chemotherapy group（HR=0.36,95%CI 0.15-0.88,P=0.039）.Conclusions1.Neoadjuvant PD-1 blockade plus chemotherapy induced a higher p CR rate than neoadjuvant chemotherapy alone,and the combined therapy was tolerable in LAGC patients.2.Neoadjuvant PD-1 blockade plus chemotherapy regimen,moderately or well differentiated adenocarcinoma,and MSI-H status were the factors that promoted p CR.3.In the patients with positive PD-L1 expressions,the recurrence-free probability was higher in neoadjuvant PD-1 blockade plus chemotherapy group.