BACKGROUND: Inhibition of the mammalian target of rapamycin (mTOR) is an established treatment for multiple malignancies. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with mTOR inhibitors. PATIENTS AND METHODS: PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2012. Eligible studies were limited to approved mTOR inhibitors (everolimus and temsirolimus) and reported on patients with cancer, randomized design and adequate safety profiles. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: In all, 3193 patients from eight randomized, controlled trials (RCTs) were included, 2236 from everolimus trials and 957 from temsirolimus trials. The relative risk (RR) of FAEs related to mTOR inhibitors use was 2.20 (95% CI, 1.25-3.90; P = 0.006) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between everolimus and temsirolimus or between tumor types [renal cell carcinoma (RCC) versus non-RCC]. No evidence of publication bias was observed. CONCLUSION: The use of mTOR inhibitors is associated with a small but higher risk of FAEs compared to control patients. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications.
BACKGROUND: Inhibition of the mammalian target of rapamycin (mTOR) is an established treatment for multiple malignancies. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancerpatients treated with mTOR inhibitors. PATIENTS AND METHODS: PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2012. Eligible studies were limited to approved mTOR inhibitors (everolimus and temsirolimus) and reported on patients with cancer, randomized design and adequate safety profiles. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: In all, 3193 patients from eight randomized, controlled trials (RCTs) were included, 2236 from everolimus trials and 957 from temsirolimus trials. The relative risk (RR) of FAEs related to mTOR inhibitors use was 2.20 (95% CI, 1.25-3.90; P = 0.006) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between everolimus and temsirolimus or between tumor types [renal cell carcinoma (RCC) versus non-RCC]. No evidence of publication bias was observed. CONCLUSION: The use of mTOR inhibitors is associated with a small but higher risk of FAEs compared to control patients. In the appropriate clinical scenario, the use of these drugs remains justified in their approved indications.
Authors: Robert Wesolowski; Mahmoud Abdel-Rasoul; Maryam Lustberg; Maria Paskell; Charles L Shapiro; Erin R Macrae Journal: Oncologist Date: 2014-05-02
Authors: Łukasz Mielczarek; Anna Brodziak; Paweł Sobczuk; Maciej Kawecki; Agnieszka Cudnoch-Jędrzejewska; Anna M Czarnecka Journal: Cancer Chemother Pharmacol Date: 2021-03-25 Impact factor: 3.333
Authors: M D Kaymakcalan; Y Je; G Sonpavde; M Galsky; P L Nguyen; D Y C Heng; C J Richards; T K Choueiri Journal: Br J Cancer Date: 2013-06-04 Impact factor: 7.640