Purpose: Targeted therapy has brought great clinical benefits for patients with multiple solid tumors, but its effects in patients with locally advanced/metastatic pancreatic cancer (LA/MPG) are disputed. This systematic evaluation compared the efficacy and safety profiles of gemcitabine combined with targeted agents (GEM + TA) versus gemcitabine administered as monotherapy or combined with placebo (GEM PLC) in LA/MPG patients. Methods: Pub Med and EMBASE were searched for relevant randomized controlled trials published on or before April 30, 2013. The primary end points were overall survival (OS) and progression-free survival (PFS); the secondary end points were 1-year survival rate, objective response rate (ORR), and toxicity rates (TRs), defined as the prevalence of grade 3/4 adverse events. The systematic evaluation was performed by using Review Manager version 5.1.7. Findings: A total of 10 randomized controlled trials involving 3899 patients (2195 males; mean age, 63.6 years) were included in the systematic evaluation. The results reported that there was no significant difference in OS (hazard ratio [HR] = 0.97 [P = 0.85]), PFS (HR = 0.95 [P = 0.14]), or ORR (odds ratio [OR] = 0.95 [P = 0.69]) between GEM + TA and GEM 11.PLC. However, a marginal difference in 1-year survival rate (OR = 0.80 [P = 0.05]) between the 2 groups was observed. The grade 3/4 TRs of anemia, diarrhea, nausea, neutropenia, thrombocytopenia, and vomiting were not significantly different between the 2 groups. However, the prevalence of grade 3/4 rash was significantly greater in the GEM + TA group (OR = 8.31 [P < 0.01]). Implications: Based on the results from this analysis, the addition of targeted agents to a regimen of gemcitabine treatment does not bring survival benefits except 1-year survival rate to patients with LA/MPG. (C) 2014 Elsevier HS Journals, Inc. All rights reserved.