Carbonic anhydrase IX (CAIX) as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma (mccRCC) in patients (pts) receiving sorafenib: Analysis of a randomized controlled trial (TARGET).

Abstract

352 Background: No biomarkers have been routinely utilized to provide guidance for treatment in mccRCC. Retrospective data analyses have suggested that CAIX may have a predictive role in pts receiving immunotherapy or vascular endothelial growth factor (VEGF)-targeted therapy (Atkins Clin Cancer Res. 2005, Choueiri BJU Int 2010). We examined the predictive value of CAIX as a biomarker in estimating treatment outcome in pts receiving sorafenib vs. placebo as part of a large randomized trial (RCT). Methods: Paraffin embedded tumor tissue was collected from 133 participants with independently reviewed disease-progression status in the TARGET study (N=903), which randomized pts to receive either sorafenib or placebo following progression on cytokine based therapy. Tumor tissue sections were immunostained for CAIX using the M75 antibody. The percentage of CAIX-positive tumor cells was assessed for each tumor by a single pathologist. The impact of CAIX expression on progression free survival (PFS, primary endpoint), and tumor shrinkage (TS) was analyzed for both sorafenib and placebo treated pts. Results: Overall, 51% of pts were intermediate and 49% low risk per MSKCC criteria. 68% had high CAIX expression (>85% cell staining). Clinical characteristics were similarly distributed between pts with low vs. high CAIX staining, as well as pts with CAIX data vs. not. Median PFS for pts with high CAIX vs. low CAIX was 5.5 months and 5.4 months respectively on the sorafenib arm (p = 0.97), and 1.5 months and 1.7 months on the placebo arm (p = 0.76). Median TS for pts with high CAIX status was −14.9% vs. −12.6% in pts with low CAIX status (p = 0.63) on the sorafenib arm, and +1.3% (high CAIX) vs. +4.8% (low CAIX) in pts on the placebo arm (p=0.60). Conclusions: Despite suggestive retrospective evidence, data from the TARGET study did not find CAIX expression status to be of predictive or prognostic value for treatment with sorafenib in pts with mccRCC following cytokine failure.