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

Publication date: August 2017
Source:European Journal of Cancer, Volume 81
Author(s): P. Penttilä, F. Donskov, J. Rautiola, K. Peltola, M. Laukka, P. Bono
BackgroundMammalian 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 methodsEighty-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.ResultsIn 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).ConclusionsEverolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy.



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