Liang Wang, Yagang Liu, Wenyong Zhou, Wei Li

To perform a systematic review and meta-analysis of Phase III randomized controlled trials (RCTs) to determine the incidence and risk of severe adverse events (AEs) with molecular targeted agents (MTAs) in advanced/metastatic gastric cancer (GC) patients. A comprehensive literature search for related trials published up to December 2015 was performed. Eligible studies were Phase III RCTs of advanced/metastatic GC patients assigned to MTAs or control group. Data were extracted by two authors for severe and fatal AEs (FAEs). A total of nine Phase III RCTs involved 4,934 GC patients were ultimately identified. The pooled results demonstrated that the addition of TAs to therapies in advanced GC significantly increased the risk of developing severe AEs (relative risk: 1.12, 95% confidence interval: 1.02-1.24, P=0.02), but not for FAEs (relative risk: 0.97, 95% confidence interval: 0.65-1.45, P=0.88). Additionally, the most common causes of FAEs with MTAs were infections (16.3%), gastrointestinal hemorrhage (8.2%), and arterial thromboembolic events (8.2%), respectively. With available evidence, the use of TAs in GC patients was associated with an increased risk of severe AEs, but not for FAE. Clinicians should be aware of the risk of severe AEs with the administration of these drugs in these patients.