Efficacy and safety of gemcitabine plus anti-angiogenesis therapy for advanced pancreatic cancer: a systematic review and meta-analysis of clinical randomized phase III trials

Purpose: Pancreatic cancer is a common digestive neoplasm with a high fatality rate. We performed this systematic review and meta-analysis of clinical randomized phase III trials to explore the efficacy and safety of gemcitabine plus anti-angiogenesis therapy versus gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Methods: We searched PubMed, Embase and the Cochrane Library to identify eligible studies. Data were collected for the period from January 1, 2000 to August 20, 2018. Hazard ratios (HRs) and odds ratios (ORs) were used as main evaluation parameters. Results: A total of eight eligible studies with 3,586 individuals were included in the present meta-analysis. The results showed that the combination of gemcitabine plus anti-angiogenesis therapy had a significant effect on progression-free survival (HR = 0.92, 95% CI: 0.86 - 1.00, P = 0.04), but led to no significant difference in the overall survival (HR = 0.96, 95% CI: 0.88 - 1.05, P = 0.38). In terms of safety, gemcitabine plus anti-angiogenesis therapy did not increase the rate of grade 3-4 common adverse effects except for hypertension. Conclusions: Although gemcitabine plus anti-angiogenesis therapy might prolong the progression-free survival in locally advanced or metastatic pancreatic cancer, these successful results did not translate into a significant improvement in the overall survival or change in the clinical guidelines.