Sunitinib Prior to Planned Nephrectomy in Metastatic Renal Cell Carcinoma: Angiogenesis Biomarkers Predict Clinical Outcome in the Prospective Phase II PREINSUT Trial.

Purpose: The PREINSUT study characterized factors predictive of response to sunitinib given before planned nephrectomy in metastatic renal-cell carcinoma (mRCC) patients. Experimental Design: This French multicentre, prospective, open-label, phase II trial (NCT00930345) included treatment-naive patients with clear-cell mRCC. Patients received two cycles of sunitinib before nephrectomy. The primary objective was to evaluate the potential of circulating angiogenesis-related biomarkers measured before and on treatment for identifying responders based on primary renal tumor (PRT) size change. Secondary objectives were to evaluate the ability of biomarkers to predict progression-free survival (PFS) and overall survival (OS). Results: Thirty-two patients were enrolled. Median PFS was 4.5 months and median OS was 12.4 months. OS was significantly longer in responding patients (28.8 vs. 11.1 months; P =0.03). Of 27 patients evaluable for PRT response, nine (33.3%) had a ³10% decrease in PRT size. Baseline biomarkers significantly associated with outcome were endothelial progenitor cells (PRT response); vascular endothelial growth factor (VEGF)-A, stromal cell-derived factor-1 (SDF-1), soluble VEGF receptors (sVEGFR)1 and 2 (PFS); and SDF‑1 and sVEGFR1 (OS). During treatment, changes in biomarkers associated with outcome were SDF-1 and platelet-derived growth factor (PDGF)-BB (PRT response); sVEGFR2 (PFS); and SDF‑1 and sVEGFR1 (OS). There was no correlation between plasma sunitinib or its active metabolite steady-state trough concentrations and clinical outcome. Conclusions: Angiogenesis-related parameters that could reflect hypoxia seem to be associated with worse outcome in mRCC. As blood biomarkers are not subjected to tumor heterogeneity and allow longitudinal follow-up, circulating angiogenesis profile has a promising place in anti-angiogenic therapy guidance.