Plasma cytokine and angiogenic factors associated with prognosis and therapeutic response to sunitinib vs everolimus in advanced non-clear cell renal cell carcinoma
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Pavlos Msaouel1,*, Amado J. Zurita1,*, Shixia Huang2, Eric Jonasch1 and Nizar M. Tannir1
1Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
2Dan L. Duncan Cancer Center & Department of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA
*These authors have contributed equally to this work
Nizar M. Tannir, email: [email protected]
Keywords: biomarkers, cytokines and angiogenic factors, everolimus, non-clear cell renal cell carcinoma, sunitinib
Received: September 20, 2016 Accepted: January 16, 2017 Published: February 02, 2017
No biomarkers are available to predict relative clinical benefit from targeted therapies in patients with non-clear cell renal cell carcinoma (nccRCC). To identify candidate predictive markers, we investigated a set of cytokines and angiogenic factors (CAFs) in previously untreated patients with nccRCC participating in the phase II ESPN trial comparing first-line sunitinib to everolimus. Pre-treatment concentrations of 30 CAFs were measured in plasma from 37 patients treated with everolimus (n=16) or sunitinib (n=21), and associated with progression-free (PFS) and overall survival (OS) after adjusting for potential confounders. High (>median) concentrations of soluble glycoprotein 130 (sgp130) were predictive of a longer PFS with sunitinib compared with everolimus (HR = 0.30; 95% CI: 0.11-0.85; P = 0.024). Significantly shorter PFS was noted, independently of treatment arm, in patients with high (>median) levels of IL-8 (HR = 3.13; 95% CI: 1.41-6.92), IL-13 (HR = 3.36; 95% CI: 1.49-7.58), and soluble tumor necrosis factor receptor II (HR = 2.21; 95% CI: 1.04-4.72). High IL-8 levels were also associated with significantly shorter OS (HR = 3.55; 95% CI: 1.55-8.14). Thus, using CAF profiling we identified candidate prognostic and predictive circulating biomarkers that can be used to inform therapeutic decisions in nccRCC.
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