1385P Transcriptome-based prognostic and predictive biomarker analysis of ENACT: A randomized controlled trial of enzalutamide (ENZA) in men undergoing active surveillance (AS)

Abstract

Men with low- or intermediate-risk prostate cancer undergo AS to avoid adverse treatment effects, but risk of disease progression remains. In the prospective randomized trial ENACT (NCT02799745), men undergoing AS who were treated with ENZA 160 mg for 1 year had a 46% reduced rate of disease progression versus AS alone (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.33, 0.89; p=0.02). Here, we assessed transcriptomic prognostic and predictive biomarkers to identify men in AS who are likely to benefit from ENZA treatment. Biomarker analyses were performed on ENACT patient samples collected at screening via Decipher GRID (Veracyte, Inc., San Francisco, CA, USA). Among 258 genomic signatures, 108 with significant interactions were evaluated. Decipher classifier was assessed for correlation with therapeutic disease progression; classifiers androgen-receptor activity (AR-A) and PAM50 were assessed for correlation with negative biopsies at year 2 (Y2). Statistical analysis was conducted by Cox proportional hazards models for disease progression, logistic regression (AR-A), and Fisher’s exact test (PAM50) for negative biopsy. Univariable and multivariable analyses were performed; univariable data is presented here. Among 95 samples analyzed (AS, n=46; ENZA, n=49), the Decipher classifier was prognostic for therapeutic disease progression in all patients (HR 1.45; 95% CI 1.04, 2.02; p=0.04). Univariable analysis showed that high AR-A and luminal PAM50 classification were predictive of ENZA response per negative biopsy at Y2 (Table).Table: 1385PBiomarkers predictive of negative biopsy at Y2 after ENZA treatmentBiomarker classifiersOR (95% CI)p valueAR-A score (per 1 increase)Interaction OR: 2.91 (0.99, 8.59)p=0.05PAM50 (luminal vs basal subtype)Treatment-effect OR Luminal:a 10.10 (1.00, 529.60) Basal:b 0.20 (0, 3.43)p=0.02aENZA: 16 patients had luminal tumors; 8/16 had a negative biopsy at Y2. AS: 12 patients had luminal tumors; 1/12 had a negative biopsy at Y2; bENZA: 11 patients had basal tumors; 1/11 had a negative biopsy at Y2. AS: 9 patients had basal tumors; 3/9 had a negative biopsy at Y2.OR=odds ratio. Open table in a new tab aENZA: 16 patients had luminal tumors; 8/16 had a negative biopsy at Y2. AS: 12 patients had luminal tumors; 1/12 had a negative biopsy at Y2; bENZA: 11 patients had basal tumors; 1/11 had a negative biopsy at Y2. AS: 9 patients had basal tumors; 3/9 had a negative biopsy at Y2. OR=odds ratio. Higher Decipher signature scores were associated with greater risk of disease progression in all patients analyzed, regardless of treatment. Biomarker signatures predictive of ENZA response included luminal tumor subtype (per PAM50) and tumors with higher AR-A scores.