A randomized phase II trial of sorafenib versus sorafenib plus low-dose interferon-alfa: Clinical results and biomarker analysis.

5093 Background: Sorafenib was shown to significantly prolong progression-free survival (PFS) in pts with mRCC after cytokine failure. We have previously shown that low-dose interferon alfa (IFN-α) was comparable in efficacy and was better tolerated than intermediate-dose IFN-α in pts with mRCC. Therefore, we sought to evaluate the benefit and toxicity of sorafenib plus low-dose (LD) IFN- α in mRCC. In addition, we assessed the ability of plasma and serum biomarkers to correlate with outcome.,Pts enrolled in this randomized phase II trial had conventional mRCC, no prior systemic therapy, PS 0/1 and no brain metastases. Only 1 patient had not undergone prior nephrectomy. Pts received sorafenib 400mg PO BID or same dose sorafenib plus LD IFN-α 0.5 million units SC BID. Primary endpoint was PFS. Plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF- bb) were measured at baseline before treatment using multiplex bead suspension arrays.,From 6/24/05 through 6/18/07, 80 pts (61 males) were enrolled (40/arm). 72 pts were evaluable for response. By Motzer et al's criteria, 52%, 46%, and 3% of pts had favorable-risk, intermediate-risk, or poor-risk prognosis, respectively. Median follow-up was 14 mos (range, 3.5- 28.7). Median PFS time for all pts was 7.4 months (95% CI, 5.5- 9.2 months). Median PFS time for the sorafenib arm was 5.7 mos (95% CI, 5.5- 9.2), compared to 7.6 mos (95% CI, 5.2-11.1) for the combination arm (P=NS). Median OS times were not reached for either arm. 6 pts on the sorafenib arm died compared to 10 pts on the combination arm. A higher percentage of pts required dose reductions or therapy discontinuation on the combination arm. PFS times for all pts were significantly longer for those pts with baseline VEGF and PDGF levels above the median (P=0.04 for both markers). The plasma levels of these two markers were positively correlated (Spearman's correlation coefficient = 0.60, P < 0.0001).,In this randomized phase II trial, there were no significant differences in efficacy between sorafenib and sorafenib plus LD IFN-α. Higher baseline VEGF and PDGF-bb levels correlated with longer PFS. Sponsored by NCI-CTEP. [Table: see text].