Association between primary tumor protein expression and response to sunitinib in patients with metastatic renal cell carcinoma.

Abstract

450 Background: Sunitinib is FDA-approved and widely used as frontline treatment for metastatic renal cell carcinoma (mRCC), but there is a large degree of variability in patient (pt) response to therapy. The association of baseline primary tumor expression of multiple proteins and objective response to sunitinib was investigated. Methods: Primary tumor samples from clear cell mRCC pts treated with sunitinib as frontline therapy at two academic institutions were retrieved. Layered immunohistochemical (LIHC) assay which allow the detection of multiple biomarkers in a single tissue section was used to evaluate the expression of 8 proteins (VEGFR1, VEGFR2, p-mTOR, p-4E-BP1 S65, VEGF A, 4E-BP1, PDGFRb, CAIX) on tumor cells. Pts were characterized as Responders (Complete Responders (CR), Partial Responders (PR) and Stable diseases (SD)) or Non-Responders (NR) based on investigator-assessment. The 8 proteins were tested separately and the area under the receiver operator characteristic (ROC) curve (AUC) analysis was used to compare the predictive power of each biomarker and their combinations. Results: 38 pts were eligible for evaluation; 29 responders and 9 non-responders. Of the 8 biomarkers tested individually, only PDGFRb and CAIX were statistically significant in providing a predictive value for response to sunitinib. Of the different possible biomarker combinations, the combination of increased levels of CAIX expression and decreased 4E-BP1 expression provided the highest ROC AUC (0.9) for predicting response. When stable disease cases were removed from the responders group, in addition to CAIX and 4E-BP1, increased levels of PDGFRb expression predicted response (AUC was 0.889). Conclusions: Baseline primary tumor expression of CAIX and 4E-BP1 is associated with an objective response to sunitinib in pts with mRCC.