Analysis Of The Efficacy And Safety Of Small Molecule Tyrosine Kinase Inhibitors Combined With Anti-PD-1 Antibody In The Treatment Of Advanced Malignant Tumor Of Digestive System

Objective: To analyze the efficacy and safety of small molecular tyrosine kinase inhibitors combined with PD-1 monoclonal antibody in the treatment of advanced malignant tumor of digestive system.Methods:The data of patients with advanced digestive system malignant tumors treated with small molecular tyrosine kinase inhibitor(TKI)combined with PD-1 monoclonal antibody in the Department of Oncology,the first affiliated Hospital of China Medical University from March 2019 to February 2021 were collected retrospectively.The time and dose of medication,adverse reactions,short-term and long-term effects were collected,and different tumor growth rates(TGR)were compared.To explore the molecular expression of T cell subsets in peripheral blood before combined treatment and the predictive effect of adverse drug reactions on the curative effect by the difference between TGR and drug efficacy.Results:A total of 30 patients with advanced digestive tract malignant tumors were included in the study,including 8 patients with second-line systemic therapy(26.67%),12 patients with third-line treatment(40.00%),and 10 patients with more than third-line treatment(33.33%).The efficacy analysis showed that the objective remission rate(ORR)and disease control rate(DCR)of 25 patients were 24.00% and 80.00%,respectively.Among them,the ORR of patients with gastric cancer and colorectal cancer was 0.00%,and the DCR was 58.33%(7/12),the ORR of patients with liver cancer was 50.00%(4/8),DCR was 100.00%),and the ORR of pancreatic cancer patients was 33.30%(1/3),DCR100.00%(3/3),the ORR of patients with esophageal cancer was 50.00%(1/2),and the DCR was 100.00%(3/3).The results of survival analysis showed that the median progression-free survival(PFS)of 25 patients was 3.99months(95%CI:3.07-4.72),and the median follow-up time was 4 months.Patients were divided into fast growth group(RG)and slow growth group(SG)according to the tumor growth rate and whether new lesions(NL)appeared in the previous first-line therapy.It was found that TGR before receiving TKI combined with PD-1 monoclonal antibody could predict the curative effect(P < 0.05,the median PFS of RG was 4.72 months,which was higher than 3.53 months of RG,and the ORR of SG was 23.08%.It was higher than that of RG(18.18%).There was no significant correlation between the molecular expression of T cell subsets in peripheral blood and the therapeutic effect before treatment.Safety analysis showed that the common adverse events(AE)mainly included albuminuria,myelosuppression,liver function injury,rash and so on.In terms of the predictive effect of adverse reactions on the curative effect,the occurrence of immune-related adverse reactions was analyzed with DCR,and the difference was statistically significant(P < 0.050).Conclusion: In the treatment of advanced digestive system cancer,small molecular tyrosine kinase inhibitors combined with PD-1 monoclonal antibody showed certain anti-tumor activity and patients with liver cancer benefited more significantly in combination therapy,and the median no progression time and ORR of patients with slow tumor growth rate were higher than those of patients with fast tumor growth rate.There was a correlation between the occurrence of immune-related adverse reactions and the curative effect.