Effects Of PD-L1 Expression,EBV And TMB On The Efficacy Of Immune Checkpoint Inhibitors In Advanced Gastric Cancer After Chemotherapy Failure

Objective:To investigate the effects of programmed death ligand 1(PD-L1)expression,Epstein-Barr virus(EBV)and tumor mutational burden(TMB)on the efficacy of immune checkpoint inhibitors in advanced gastric cancer patients who failed chemotherapy.Methods:We collected 37 patients with advanced gastric cancer who had failed previous chemotherapy with immune checkpoint inhibitors(ICIs)combined with chemotherapy or targeted agents at the Second Affiliated Hospital of Nanchang University from June2019 to September 2021.PD-L1 expression and TMB level were detected by nextgeneration sequencing(NGS),and EBV infection status was detected by in situ hybridization(IHC).Combined positive score(CPS)was used to assess PD-L1 expression.According to the test results,they were divided into PD-L1 positive expression(CPS≥1)and PD-L1 negative expression(CPS <1),TMB-H(≥10 mut/Mb),and TMB-L(<10 mut/Mb),EBV+ and EBV-.We compared the progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and disease control rate(DCR)under different conditions of patients to explore the effects of the above indicators on the efficacy of immune checkpoint inhibitors in the treatment of advanced gastric cancer.Results:1.Short-term efficacy results: The ORR of patients with PD-L1 positive expression(n=17)and negative expression(n=20)were 29.4% and 20.0%(P=0.703),and the DCR were 76.5% and 60.0%(P=0.319),the difference was not statistically significant.The ORR of EBV+(n=2)and EBV-(n=35)were 50.0% and 20.0%,and the DCR were 100.0% and 65.7%.The ORR of TMB-H(n=10)group and TMB-L(n=17)group was 40.0% and 18.5%(P=0.215),and the DCR was 90.0% and 59.3%(P=0.119),the difference was not statistically significant.2.Long-term efficacy results: The m PFS of patients with positive and negative PD-L1 expression was 5.5 months and 3.0 months(P=0.009),and the m OS was 14.6months and 9.5 months(P=0.015).The difference was statistically significant.The PFS of the first EBV-positive patient was 5 months and the OS was 9.5 months;the PFS of the second EBV-positive patient was 7.6 months and the OS was 15 months.The m PFS of TMB-H and TMB-L patients was 5 months and 3.2 months(P=0.104),and the m OS was 12.0 months and 8.5 months(P=0.433),and the difference was not statistically significant.The COX analysis of the factors that may affect PFS and OS showed that the main factors affecting PFS were PD-L1 positive expression and peritoneal metastasis,and PD-L1 positive expression was also an important factor affecting OS.Conclusions:Compared with the PD-L1-negative group,PD-L1-positive advanced gastric cancer patients have longer m PFS and m OS,and may benefit more from the long-term efficacy of immune checkpoint inhibitor therapy.There was no significant correlation between TMB levels and the efficacy of immune checkpoint inhibitors.There are few EBV-positive samples,and the impact on immune checkpoint inhibitors cannot be judged.