Four trials were performed in patients with RCC, three in patients with breast cancer, two in patients with neuroendocrine tumors, two in patients with SCLC and one in patients with advanced solid tumors. The 12 included trials were published in 2004–2012. The median age of study GSK 789472 hydrochloride participants was in the range of 55–68 years. Sample sized were in the range of 24 to 724 patients, with eight trials including.100 patients each. Six trials were randomized controlled trials, while the others were prospective phase II trials. The dosage of mTOR inhibitors significantly varies among included trials: temsirolimus was used ranging from 20 mg to 250 mg iv weekly, and the dose of everolimus was 10 mg or 5 mg po. daily, respectively. The quality of 12 included trials was high: five trials had Jadad scores of 5, which mentioned the concealment of allocation clearly in the randomization process, and provided the number of patients who withdrew from the trials. Although cytotoxic chemotherapy has still been the mainstay for cancer treatment, advances in the knowledge of tumor biology and the molecular pathways involved in cancer cell proliferation have ushered the age of molecularly targeted agents for cancer treatment. In contrast with traditional cytotoxic agents, these agents offer the promise of improved efficacy and a more favorable toxicity prolife. However, unique common side effect profile of these GR 127935 hydrochloride agents including hypertension, rashes, and metabolic abnormalities has also been reported in clinical trials. The incidence and management algorithms for those common side effects have been well defined in previous researches, but there is much more challenging to appreciate the uncommon, yet serious, toxicities associated with these drugs. The meta-analysis is a powerful statistical tool to estimate the incidence and risk of those uncommon serious drug-related toxicities and this approach has been utilized to demonstrate an increased risk in treatment related mortality with bevacizumab and VEGFR-TKIs in previous researches. To the best of our knowledge, this is the first meta-analysis to investigate the incidence and risk of FAE associated with the mTOR inhibitors everolimus and temsirolimus. Our meta-analysis included 3322 patients from 12 trials demonstrates the overall incidence rate of FAEs is 1.8%, and there is a significant threetimes increased risk of death with these agents. However, a nonsignificantly increased risk of mTOR inhibitor associated FAEs is observed in sub-group analysis according to the mTOR inhibitors, tumor types and controlled therapy, for which we suggest several possible explanations: the small number of events recorded; underreporting of rare adverse events; the fact that clinical trials are usually not designed specifically to address toxic events; and the small number of randomized controlled trials included. As mTOR inhibitors find more clinical applications and are used to treat a more heterogeneous patient population than those found in clinical trials, efforts are still needed to limit the risk of FAEs.