In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters.
Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment).
Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category.
A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.British Journal of Cancer advance online publication, 6 July 2017; doi:10.1038/bjc.2017.206 www.bjcancer.com.
British journal of cancer. 2017 Jul 06 [Epub ahead of print]
A J Zurita, R C Gagnon, Y Liu, H T Tran, R A Figlin, T E Hutson, A M D'Amelio, C N Sternberg, L N Pandite, J V Heymach
MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA., Bristol-Myers Squibb Company, PO Box 5400, J42-05, Princeton, NJ 08543, USA., Pfizer Translational Oncology, 10646 Science Center Dr, San Diego, CA 92121, USA., Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA 90048, USA., US Oncology/McKesson Specialty Health, The Woodlands, TX, USA., Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, USA., Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome 00152, Italy., Adaptimmune LLC, Philadelphia, PA 19112, USA.