Identifying molecular determinants of response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the SPARTAN trial.

Abstract

42 Background: The SPARTAN trial recently demonstrated that addition of APA to androgen deprivation therapy (ADT) improved metastasis-free survival (MFS) and second progression-free survival (PFS2) in nmCRPC pts. We performed transcriptome-wide profiling of available primary tumor samples from pts in SPARTAN to evaluate potential biomarkers of response or resistance to APA+ADT. Methods: Pts included in SPARTAN were at high risk of developing metastasis.We used a commercially available genomic assay (DECIPHER prostate test, GenomeDx Biosciences, Inc., San Diego, CA) to assess gene expression in 233 archived primary tumors from SPARTAN pts. Using a Cox proportional hazard model, we assessed the association between scores and subtypes from previously derived prognostic and predictive gene signatures, such as DECIPHER and basal (BA) vs luminal (LU) subtyping. Results: Pts with high DECIPHER scores had greater treatment effect with APA+ADT than those with low scores. Pts with LU, a subtype known to be sensitive to ADT, greatly benefited from APA+ADT. Pts with BA, typically resistant to ADT, also benefited from APA+ADT. Conclusions: DECIPHER score and BA or LU subtype may be biomarkers of response to APA+ADT. DECIPHER may be useful for identifying pts for early treatment intensification with APA or other agents, and molecular subtyping may be an effective approach for pt selection in trials combining novel therapies with APA. Clinical trial information: NCT01946204. [Table: see text]