Efficacy And Safety Of Target Drug As Second Line Treatment For Advanced Gastric Cancer : A Meta Analysis

Objective: At present,the results of clinical studies on second-line targeted therapy for advanced gastric cancer show that survival benefit,clinical efficacy and adverse reactions are controversial.And there is no comprehensive research on second-line treatment of advanced gastric cancer.The purpose of this study was to evaluate the efficacy and safety of molecular targeted drugs as the secondline therapy for advanced gastric cancer.To provide a new way for the secondline treatment of advanced gastric cancer to guide the clinical practice.Methods: To search for the clinical study of targeted drugs as the second line treatment for advanced gastric cancer,we searched the English reference on PubMed,Web of Science and Cochrane Library,and searched the Chinese reference on Chinese National Knowledge Infrastructure,Chinese Biological Medical Database,Wanfang Database and VIP Chinese Science & Technology Journal Database,The time limit for retrieval is from the construction of the database to January 2018.The literature screening and data extracted were conducted independently by two researchers,targeted drug monotherapy with or witout chemotherapy as the observation group,chemotherapy or placebo as the control group,the risk of literature bias included in the study will be assessed according to Cochrane handbook 5.1,and the quality of the literature will be evaluated with Jadad Scale.Meta-analysis was implemented using Stata 12.0 and RevMan 5.3 logiciel.Results: A total of 3511 patients were included in this study.All the studies were randomized controlled trials.1990 patients were involved in the observation group and 1521 in the control group.In terms of survival benefits,the OS of the targeted treatment group was significantly longer than that of the control group,HR=0.86,95%CI(0.80,0.93),P<0.0001.But there was no significant difference of PFS in the two groups,HR=0.83,95%CI(0.67,1.02),P=0.077?In terms of effectiveness,the ORR of the targeted treatment group was significantly better than that of the control group,0R=1.95,95%CI(1.30,2.92),P=0.001.But In terms of disease control,there is no sufficient evidence that there is a clear difference between the two groups,0R=1.39,95%CI(0.91,2.13),P=0.13.To the Side effects,The risk of grade 3~4 adverse events in the target group was significantly higher than that in the control group,0R=1.65,95%CI(1.14,2.93),P=0.0.08,Especially diarrhea(0R=2.79,95%CI(1.56-4.97),P=0.0005)and fatigue(0R=1.50,95%CI(1.12-2.02,P=0.007).Conclusion: The total survival benefit and Objective response rate of disease of the targeted treatment group was better than that of the control group,but there was no significant difference in the Progression-free survival and Disease control rate.The adverse events of grade 3~4 were significantly higher in the targeted treatment group than in the control group,especially diarrhea and fatigue.The targeted therapy may be considered as a second line treatment for advanced gastric cancer after the failure in first-line treatment,but the multi-center and large sample clinical trial is still multi-center and large sample needed to verify it.