ESMO 2022: Transcriptome-Based Prognostic and Predictive Biomarker Analysis of ENACT: A Randomized Controlled Trial of Enzalutamide (ENZA) in Men Undergoing Active Surveillance (AS)

(UroToday.com) In the Prostate Cancer poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Ashley Ross presented a transcriptome-based assessment of prognostic and predictive biomarkers among patients in the ENACT trial of enzalutamide in patients undergoing active surveillance for prostate cancer. While active surveillance is widely used and recommended for men with low- or intermediate-risk prostate cancer in order to avoid adverse treatment effects. However, there is a not insignificant risk of disease progression that remains. The randomized ENACT trial (NCT02799745) assessed whether one year of enzalutamide could reduce disease progression, 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). However, there are downsides in terms of cost and toxicity to the use of enzalutamide, thus, optimizing patient selection is key. In this analysis, the authors assessed transcriptomic prognostic and predictive biomarkers to identify men in AS who are likely to benefit from enzalutamide treatment.

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The authors used the Decipher GRID platform (Veracyte, Inc., San Francisco, CA, USA) to perform biomarker analyses among samples collected at screening among patients in the ENACT trial.

Among 258 genomic signatures, 108 with significant interactions were evaluated. In particular, the authors used:

  • the Decipher classifier to assess for correlation with therapeutic disease progression;
  • classifiers of androgen-receptor activity (AR-A) and PAM50 to assess for correlation with negative biopsies at year 2.

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.

The authors examined 95 samples among 46 patients who received active surveillance along and 49 who received enzalutamide. Among all patients, the Decipher classifier was prognostic for therapeutic disease progression (HR 1.45; 95% CI 1.04, 2.02; p=0.04). Additionally, both a high AR-A and luminal PAM50 classification were predictive of response to enzalutamide.

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Dr. Ross, therefore, concluded that biomarker signatures were associated with overall disease progression as well as predictive of the benefit of enzalutamide in patients undergoing active surveillance.

Presented by: Ashley Ross, MD, Ph.D., Associate Professor, Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.