title: Rash to the mTOR inhibitor everolimus: systematic review and meta-analysis.
abstract: BACKGROUND
  Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for treatment of renal cell carcinoma, subependymal giant cell astrocytoma, breast cancer, and progressive neuroendocrine tumors of pancreatic origin. Its use may be hindered because of adverse events, including rash. The reported incidence and risk of a rash to everolimus varies widely and has not been closely investigated. Therefore, we conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing a rash.
  
  
  METHODS
  We searched PubMed and Web of Science databases and abstracts presented at the American Society of Clinical Oncology from 1998 to December 2011 using the keyword "everolimus" to identify relevant clinical trials. Eligible studies included prospective phase II and III clinical trials of cancer patients on 10 mg of everolimus daily with available data on incidence of rash. The summary incidence and relative risk (RR) of rash were calculated using either the random-effects or fixed-effects model, depending on the heterogeneity of the constituent studies.
  
  
  RESULTS
  A total of 2242 patients with various malignancies from 13 clinical trials were included in the analysis. The summary incidences of all-grade and high-grade rash in patients on everolimus were 28.6% [95% confidence interval (CI), 20.8-38.0] and 1.0% (95% CI, 0.6-1.8), respectively. Everolimus was associated with a statistically significant increased risk of all-grade rash (RR=3.853, 95% CI, 2.470-6.013, P=0.000), but the RR for high-grade rash (RR=2.997, 95% CI, 0.633-14.185) was not statistically significant, with a P value of 0.166.
  
  
  CONCLUSIONS
  Everolimus is associated with a significant risk of developing a rash. Management of rash to everolimus is critical to prevent dose modifications and decreased quality of life, both of which can negatively affect overall clinical outcomes.
authors.affiliation: *Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA †Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York §Stony Brook University Medical School, Medical Oncology, Stony Brook, NY ‡Department of Dermatology, Hospital Santa Casa de Misericórdia de Curitiba/PUC-PR, Curitiba, PR, Brazil.
authors.forename: Marigdalia K
authors.initials: MK
authors.lastname: Ramirez-Fort
authors.forename: Emily C
authors.initials: EC
authors.lastname: Case
authors.forename: Alyx C
authors.initials: AC
authors.lastname: Rosen
authors.forename: Felipe B
authors.initials: FB
authors.lastname: Cerci
authors.forename: Shenhong
authors.initials: S
authors.lastname: Wu
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D015986:Confounding Factors, Epidemiologic; D003875:Drug Eruptions / Q000453:epidemiology* / Q000209:etiology*; D000068338:Everolimus; D006801:Humans; D015994:Incidence; D011788:Quality of Life; D012306:Risk; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus