title: Clinical experience and critical evaluation of the role of everolimus in advanced renal cell carcinoma.
abstract: The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR), was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001). Placebo crossovers (80%) contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a sequentially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor failure resulted in an even longer progression-free survival time (5.4 months) than in the entire population (4.9 months). These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated.
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.forename: Jan
authors.initials: J
authors.lastname: Schmitges
authors.forename: Claudio
authors.initials: C
authors.lastname: Jeldres
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Paul
authors.initials: P
authors.lastname: Perrotte
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
keywords: everolimus; mTOR; metastatic renal cell carcinoma; sequential therapy; targeted therapy