Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma.
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).
White
Dorothy A
DA
Memorial Sloan-Kettering Cancer Center, Pulmonary Medicine, New York, NY 10021, USA. whited@mskcc.org
Camus
Philippe
P
Endo
Masahiro
M
Escudier
Bernard
B
Calvo
Emiliano
E
Akaza
Hideyuki
H
Uemura
Hirotsugu
H
Kpamegan
Euloge
E
Kay
Andrea
A
Robson
Matthew
M
Ravaud
Alain
A
Motzer
Robert J
RJ
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
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus