title: Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer: A Meta-Analysis of 10 Randomized Controlled Trials.
abstract: The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC).A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0).Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78-0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72-0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27-1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups.In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens.
authors.affiliation: From the Department of General Surgery, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.forename: Xiao-Tian
authors.initials: XT
authors.lastname: Huang
authors.forename: Yan-Song
authors.initials: YS
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhou-Lu
authors.initials: ZL
authors.lastname: Liu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents