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Clinical Trial
. 2014 Jan;73(1):151-61.
doi: 10.1007/s00280-013-2333-4. Epub 2013 Nov 13.

Circulating proteins as potential biomarkers of sunitinib and interferon-α efficacy in treatment-naïve patients with metastatic renal cell carcinoma

Charles S Harmon  1 , Samuel E DePrimo, Robert A Figlin, Gary R Hudes, Thomas E Hutson, M Dror Michaelson, Sylvie Négrier, Sindy T Kim, Xin Huang, J Andrew Williams, Tim Eisen, Robert J Motzer
Affiliations
Clinical Trial

Circulating proteins as potential biomarkers of sunitinib and interferon-α efficacy in treatment-naïve patients with metastatic renal cell carcinoma

Charles S Harmon et al. Cancer Chemother Pharmacol. 2014 Jan.

Abstract

Purpose: We investigated potential biomarkers of efficacy in a phase III trial of sunitinib versus interferon-alpha (IFN-α), 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-α 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-α (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-α 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-α 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.

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Figures

Fig. 1
Fig. 1
Change in biomarker [vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8 (IL-8) and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3)] levels during treatment in the a sunitinib arm and b interferon-alpha arm. *P < 0.05; **P < 0.01; ***P < 0.0001 compared with baseline
Fig. 2
Fig. 2
Sunitinib arm: a progression-free and b overall survival after stratification by median baseline plasma soluble vascular endothelial growth factor receptor-3 (sVEGFR-3)
See this image and copyright information in PMC

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