title: Treatment-related mortality with everolimus in cancer patients.
abstract: BACKGROUND
  The overall incidence and odds of fatal adverse events (FAEs) after exposure to everolimus are not well defined. We performed a comprehensive meta-analysis of published randomized controlled trials (RCTs) to determine the role of everolimus in treatment-related mortality in patients with cancer.
  
  
  METHODS
  PubMed databases and abstracts from the proceedings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were searched for RCTs of everolimus either alone or in combination with another agent compared with the control arm without everolimus and that reported deaths from an adverse event from January 1966 to July 2013. The primary objective was to determine the difference of FAEs between everolimus-treated patients and control group patients.
  
  
  RESULTS
  In total, 2,997 patients with multiple solid tumors from nine RCTs were included. The overall incidence of FAEs in cancer patients treated with everolimus was 0.7% (95% CI 0.3%-1.1%) compared with 0.4% (95% CI 0.0%-0.7%) in cancer patients who did not receive everolimus. The odds ratio of FAEs was greater in everolimus-treated patients (Peto odds ratio = 3.80, 95% CI 1.59-9.07, p = .003). In subgroup analyses, no significant difference was found in the incidence or odds of FAEs by everolimus administration (alone or in combination) or tumor type (breast cancer vs. nonbreast cancer; p = .63).
  
  
  CONCLUSIONS
  In patients with cancer, everolimus is associated with a small but significant increase in the odds of a treatment-related fatal events.
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wesolowski
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdel-Rasoul
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Lustberg
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Paskell
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
authors.affiliation: The James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA erin.macrae@osumc.edu.
authors.forename: Erin R
authors.initials: ER
authors.lastname: Macrae
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions / Q000401:mortality*; D000068338:Everolimus; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010361:Patients; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D020123:Sirolimus
keywords: Adverse events; Cancer; Everolimus; Meta-analysis; Mortality