title: A prospective observational study on the evaluation of everolimus-related adverse events in metastatic renal cell carcinoma after first-line anti-vascular endothelial growth factor therapy: the AFINITE study in France.
abstract: The objective of the study was to describe the occurrence of stomatitis and noninfectious lung disease in patients with metastatic renal cell carcinoma (mRCC) treated with second-line everolimus in a real-world setting.
  
  
  
  This multicenter, prospective, observational study was conducted in France by physicians with experience of treatment of patients with mRCC. Patients aged ≥18 years who received everolimus after first-line antivascular endothelial growth factor (VEGF) therapy were included in the study. The primary safety assessments were occurrence of stomatitis (in terms of severity, event dates, and therapeutic management) and noninfectious pneumonitis (in terms of detection methodology, severity, event dates, and therapeutic management).
  
  
  
  Between September 2010 and August 2012, 284 patients were enrolled at 77 centers, of whom, 274 received everolimus therapy. Most patients had mRCC of clear cell histology (88%), and most of them (84%) received first-line sunitinib. In total, 40% of patients experienced treatment-related stomatitis, and 15% of patients experienced noninfectious lung disease. Most of them had a single episode. The incidence of grade 3 stomatitis and noninfectious lung disease were 8 and 3%, respectively. Mean time to the first episode was 27 days for stomatitis and 72 days for noninfectious lung disease from treatment initiation. Stomatitis and noninfectious lung disease resulted in treatment discontinuations in 2 and 7% of patients, respectively. The primary first-episode treatment was mouthwash (86%) for stomatitis and corticosteroids (65%) for noninfectious lung disease.
  
  
  
  This study confirms that stomatitis and noninfectious lung disease are commonly associated with everolimus use. Both adverse events were rarely severe and were managed easily and efficiently.
authors.affiliation: Centre François Baclesse-CHU, Caen, France. f.joly@baclesse.unicancer.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Institut Jean Godinot, Reims, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Eymard
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Hôpital Jean Minjoz (Besançon), Saint Priest en Jarez Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Institut de Cancérologie Lucien Neuwirth, Saint Priest en Jarez, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Guillot
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO), Saint Herblain, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Rolland
authors.affiliation: Centre d'Oncologie de Gentilly, Nancy, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Spaeth
authors.affiliation: Centre Eugène Marquis, Rennes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laguerre
authors.affiliation: Hôpital Foch, Suresnes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lebret
authors.affiliation: Novartis France, Rueil-Malmaison, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kelkouli
authors.affiliation: Novartis France, Rueil-Malmaison, France.
authors.forename: Khemaies
authors.initials: K
authors.lastname: Slimane
authors.affiliation: CHU Bordeaux, Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000188:drug therapy; D000068338:Everolimus / Q000009:adverse effects*; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068338:Everolimus
keywords: Everolimus; Metastatic renal cell carcinoma; Noninfectious lung disease; Stomatitis