Meta-analysis of Phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer

Objectives: For patients with unresectable pancreatic cancer (PC), the efficacy and safety of molecular targeted agents (MTAs) in combination with gemcitabine are still unclear. Published randomized controlled trials (RCTs) have reported conflicting results. This study aimed to conduct a systematic review of the literature and to perform a meta-analysis if appropriate. Methods: Seven electronic databases were searched using a standard technique to November 2011 without restriction on publication status or language. The primary aim was to assess overall survival (OS). Secondary aims were to assess progression-free survival (PFS), overall response rates (ORRs) and grade 3, 4 and 5 toxicities. A random-effects model was used for the meta-analysis. Results: Seven Phase III RCTs were identified; 1981 patients were treated with MTAs and gemcitabine, and 1992 patients received gemcitabine with or without placebo. No statistically significant difference in OS was found between the two groups [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.85-1.02; P = 0.13]. The addition of MTAs improved PFS (HR = 0.86, 95% CI 0.79-0.93; P = 0.000) and ORR (odds ratio 1.35, 95% CI 1.05-1.74; P = 0.01). However, these benefits were accompanied by significantly higher toxicity (P = 0.001). Conclusions: The findings of this study suggest that the palliation of PC with gemcitabine and MTAs does not provide a significant survival benefit and is associated with increased grade 3 and 4 toxicities.