Abstract 1385P
Background
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.
Methods
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.
Results
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: 1385P
Biomarkers predictive of negative biopsy at Y2 after ENZA treatment
| Biomarker classifiers | OR (95% CI) | p value |
| AR-A score (per 1 increase) | Interaction OR: 2.91 (0.99, 8.59) | p=0.05 |
| PAM50 (luminal vs basal subtype) | Treatment-effect OR Luminal:a 10.10 (1.00, 529.60) Basal:b 0.20 (0, 3.43) | |
| p=0.02 |
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.
Conclusions
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.
Clinical trial identification
NCT02799745.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Terrance Ku, MSc, Nicholas Strange, BA, and Jane Beck, MA from Complete HealthVizion, funded by the study sponsors.
Legal entity responsible for the study
Astellas Pharma Inc.; Pfizer Inc.
Funding
This study was funded by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide.
Disclosure
A. Ross: Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma Inc., Bayer, Blue Earth, Janssen, Pfizer, Myovant, Veracyte/Decipher, Lantheus; Financial Interests, Personal, Advisory Board: Astellas Pharma Inc., Bayer, Janssen; Financial Interests, Personal, Advisory Role: Astellas Pharma Inc., Bayer, Blue Earth, Janssen, Pfizer, Myovant, Veracyte/Decipher, Lantheus. K.K. Iwata, D. Elsouda, J. Hairston: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Inc. D. Russell: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. E. Davicioni: Financial Interests, Personal, Full or part-time Employment: Veracyte, Inc. J.A. Proudfoot: Financial Interests, Personal, Full or part-time Employment: Veracyte, Inc.; Financial Interests, Personal, Stocks/Shares: Veracyte, Inc. N.D. Shore: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, BMS, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, Genesis Care, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer Inc., Phosphorous, Propella, PreView, Sanofi Genzyme, Specialty Networks, Sensen Bio, Tolmar, UroGen; Financial Interests, Personal, Expert Testimony: Ferring. M.R. Cooperberg: Financial Interests, Personal, Advisory Role: Dendreon, AstraZeneca, Veracyte, Foundation Medicine, Exact Sciences, Exelixis, Bayer, Merck, Janssen. All other authors have declared no conflicts of interest.