Efficacy and safety of gemcitabine-targetedagent combination therapy in advanced pancreaticcancer: a meta-analysis of randomized controlled trials

摘要

Objective: A meta-analysis was performed to compare the clinical efficacy and safety of gemcitabinein combination with targeted agents versus gemcitabine alone in advanced pancreatic cancer (APC). Methods:PubMed, EMBASE and Cochrane Library databases were searched to find relevant clinical trials which were designedto investigate targeted agents in the treatment of APC patients (up to October 2017). The end-points includedoverall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity rate. Publicationbias was evaluated by Egger’s test and funnel plots. Results: Twenty-eight trials involving a total of 8858 volunteerswere selected for the meta-analysis. No significant difference was found in OS (HR = 0.969, 95% CI: 0.922-1.019,P = 0.217) and ORR (OR = 1.053, 95% CI: 0.799-1.388, P = 0.714) between targeted agents plus gemcitabine andgemcitabine alone. Targeted agents plus gemcitabine had significant but marginal benefit in PFS (HR = 0.923, 95%CI: 0.876-0.974, P = 0.003) compared with gemcitabine alone. Targeted agents added to gemcitabine significantlyincreased the grade 3-4 neutropenia, thrombocytopenia, diarrhoea and rash compared with gemcitabine alone. Thefunnel plot presented substantial symmetry and showed little evidence of publication bias. Conclusions: Based onthe outcomes of this analysis, addition of targeted agents to gemcitabine did not improve the OS and ORR of APCpatients, and significantly but marginally increased their PFS. So the clinical efficacies of targeted agents need tobe further investigated using other treatment strategies.