Abstract
36 Background: Sip-T is an FDA-approved immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). While baseline prostate-specific antigen level correlates with prolonged OS in pts treated with sip-T, biomarkers predictive of OS remain elusive. Gene expression signatures in peripheral blood (PB) correlate with prognosis in mCRPC (Ross et al, Lancet Oncol. 2012). This study sought to identify a candidate PB gene signature predictive of OS benefit with sip-T. Methods: PB mononuclear cells from sip-T or control (CN) mCRPC pts in the IMPACT trial (NCT00065442) were collected prior to leukapheresis. Affymetrix gene chip (HGU133P2) screening evaluated gene expression; association of gene expression with OS was performed using a multivariate Cox proportional hazards regression model, where OS was fit to gene expression and the 2003 baseline Halabi prognostic variables. The top 50 gene candidates were selected for qPCR confirmation. Results: Out of the 50 gene candidates selected for qPCR confirmation, 5 genes were associated with OS. High expression of SNTB1 and CHI3L2 and low expression of SYNGR3, AURKC, and ZNF268 were associated with improved OS in sip-T–treated pts but not in CN arm pts. A composite gene score (CGS) was calculated incorporating expression of these genes. In a CGS tertile analysis, OS in the top and middle sip-T tertiles was significantly better compared with the corresponding CN groups (Table). The lowest sip-T tertile had a median OS similar to that of the CN arm. Conclusions: CGS based on baseline gene expression may predict OS outcomes for mCRPC pts receiving sip-T. Compared with the CN arm, OS was significantly improved in the top two tertiles of sip-T–treated pts; OS in the bottom tertile was similar to the CN arm. Clinical trial information: NCT00065442. [Table: see text]
Published Version
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