title: Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma.
abstract: BACKGROUND
  Noninfectious pneumonitis is a known class effect of mammalian target of rapamycin (mTOR) inhibitors.
  
  
  OBJECTIVE
  To assess the incidence, radiographic patterns, management, and outcome of pneumonitis in patients with advanced renal cell carcinoma receiving everolimus.
  
  
  METHODS
  Clinical study data from 416 patients, randomized to receive everolimus versus placebo, were analyzed for adverse events of pneumonitis. Radiographic studies performed every 8 weeks were subject to a prospective, independent, blinded central review for the presence of findings indicative of pneumonitis.
  
  
  RESULTS
  Of 274 patients receiving everolimus, clinical pneumonitis was suspected for 37 patients (13.5%) (none with placebo). Nine cases (3.3%) were grade 1 (asymptomatic), 18 (6.6%) were grade 2 (not interfering with daily living), and 10 (3.6%) were grade 3 (interfering with daily living or oxygen indicated). No grade 4 (life-threatening) pneumonitis was observed. Of the 10 patients with grade 3 pneumonitis, 5 had baseline radiological evidence of pneumonitis before everolimus therapy. Twenty of the 37 cases (54.0%) were reversible within the follow-up period; resolution followed dose reduction for 20 patients and treatment discontinuation in 10 patients. Corticosteroid therapy was initiated in 16 cases. Dedicated radiological review of available serial radiographic studies (245 patients receiving everolimus and 132 receiving placebo) found a higher percentage of new radiographic findings even in patients without a diagnosis of clinical pneumonitis who were receiving everolimus versus placebo (38.9 vs. 15.2%).
  
  
  CONCLUSIONS
  Early recognition, prompt intervention, and a conservative approach are important in managing the risk associated with noninfectious pneumonitis in association with everolimus. Clinical trial registered with www.clinicaltrials.gov (NCT 00410124).
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Pulmonary Medicine, New York, NY 10021, USA. whited@mskcc.org
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: White
authors.forename: Philippe
authors.initials: P
authors.lastname: Camus
authors.forename: Masahiro
authors.initials: M
authors.lastname: Endo
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Emiliano
authors.initials: E
authors.lastname: Calvo
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Euloge
authors.initials: E
authors.lastname: Kpamegan
authors.forename: Andrea
authors.initials: A
authors.lastname: Kay
authors.forename: Matthew
authors.initials: M
authors.lastname: Robson
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014057:Tomography, X-Ray Computed
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus