FCCC LOGO Faculty Publications
Harmon CS , DePrimo SE , Figlin RA , Hudes GR , Hutson TE , Michaelson MD , Negrier S , Kim ST , Huang X , Williams JA , Eisen T , Motzer RJ
Circulating proteins as potential biomarkers of sunitinib and interferon-alpha efficacy in treatment-naive patients with metastatic renal cell carcinoma
Cancer Chemother Pharmacol. 2014 Jan;73(1) :151-61
PMID: 24220935    PMCID: PMC3889677    URL: https://www.ncbi.nlm.nih.gov/pubmed/24220935
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Abstract
PURPOSE: We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-alpha), first-line in metastatic renal cell carcinoma (mRCC), by analyzing plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, soluble VEGF receptor-3 (sVEGFR-3) and interleukin (IL)-8. METHODS: Seven hundred and fifty mRCC patients were randomized to oral sunitinib 50 mg/day in repeated cycles of a 4-week on/2-week off schedule or IFN-alpha 9 million units subcutaneously thrice weekly. Plasma samples collected from a subset of 63 patients on days 1 and 28 of cycles 1-4 and at end of treatment were analyzed by ELISA. RESULTS: Baseline characteristics of biomarker-evaluated patients in sunitinib (N = 33) and IFN-alpha (N = 30) arms were comparable to their respective intent-to-treat populations. By univariate Cox regression analysis, low baseline soluble protein levels were associated with lower risk of progression/death (all P < 0.05): in both treatment arms, baseline VEGF-A and IL-8 were associated with overall survival (OS) and baseline VEGF-C with progression-free survival (PFS); in the sunitinib arm, baseline VEGF-A was associated with PFS and baseline sVEGFR-3 with PFS and OS; in the IFN-alpha arm, baseline IL-8 was associated with PFS. In multivariate analysis, baseline sVEGFR-3 and IL-8 remained independent predictors of OS in the sunitinib arm, while no independent predictors of outcome remained in the IFN-alpha arm. Pharmacodynamic changes were not associated with PFS or OS for any plasma protein investigated. CONCLUSIONS: Our findings suggest that, in mRCC, baseline VEGF-A and IL-8 may have prognostic value, while baseline sVEGFR-3 may predict sunitinib efficacy.
Notes
Harmon, Charles S DePrimo, Samuel E Figlin, Robert A Hudes, Gary R Hutson, Thomas E Michaelson, M Dror Negrier, Sylvie Kim, Sindy T Huang, Xin Williams, J Andrew Eisen, Tim Motzer, Robert J eng Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Germany Cancer Chemother Pharmacol. 2014 Jan;73(1):151-61. doi: 10.1007/s00280-013-2333-4. Epub 2013 Nov 13.