Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

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Penttila , P , Donskov , F , Rautiola , J , Peltola , K , Laukka , M & Bono , P 2017 , ' Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma ' , European Journal of Cancer , vol. 81 , pp. 9-16 . https://doi.org/10.1016/j.ejca.2017.05.004

Title: Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma
Author: Penttila, P.; Donskov, F.; Rautiola, J.; Peltola, K.; Laukka, M.; Bono, P.
Contributor: University of Helsinki, Clinicum
University of Helsinki, Department of Oncology
University of Helsinki, University of Helsinki
Date: 2017-08
Language: eng
Number of pages: 8
Belongs to series: European Journal of Cancer
ISSN: 0959-8049
URI: http://hdl.handle.net/10138/297790
Abstract: Background: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. Patients and methods: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. Results: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P <0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P <0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P <0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). Conclusions: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy. (C) 2017 Elsevier Ltd. All rights reserved.
Subject: mTOR-inhibitor
Everolimus
Pneumonitis
NONINFECTIOUS PNEUMONITIS
NEUROENDOCRINE TUMORS
PULMONARY TOXICITY
MTOR INHIBITORS
PHASE-3 TRIAL
OPEN-LABEL
CANCER
MANAGEMENT
THERAPY
BIOMARKERS
3122 Cancers
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