Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes.
OBJECTIVE
To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC).


METHODS
Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis.


RESULTS
NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis.


CONCLUSIONS
There was an increased incidence of NIP in everolimus-treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.
Department of Pharmacy Clinical Programs, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bradley J
BJ
Atkinson
Diana H
DH
Cauley
Chaan
C
Ng
Randall E
RE
Millikan
Lianchun
L
Xiao
Paul
P
Corn
Eric
E
Jonasch
Nizar M
NM
Tannir
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D000068338:Everolimus; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000627:therapeutic use; D011014:Pneumonia / Q000139:chemically induced* / Q000628:therapy; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001993:Bronchodilator Agents; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D010100:Oxygen; D020123:Sirolimus
everolimus; pneumonitis; renal cell carcinoma (RCC); temsirolimus