Prostate cancer genomic tests show prognostic value for progression, therapy benefit

Data from a preplanned analysis of the phase 2 ENACT trial (NCT02799745) indicate that the Decipher Prostate Genomic Classifier may be prognostic for disease progression among patients with low- to intermediate-risk prostate cancer undergoing active surveillance (AS).¹

Among patients treated with enzalutamide, 50% of those who had luminal tumors had a negative biopsy at year 2, compared with 9% of those with basal tumors.

Findings also suggested that higher Decipher scores, greater androgen receptor activity (AR-A) scores, and luminal tumor subtypes in the Prediction Analysis of Microarray 50 (PAM50) cell subtype signature may serve as biomarkers for patients undergoing active surveillance who are likely to respond to treatment with enzalutamide (Xtandi).

“The findings from the ENACT trial analysis demonstrate that the Decipher Prostate test is a predictor of disease progression on AS,” said Elai Davicioni, PhD, Veracyte’s medical director for Urology, in a news release on the findings.² “These data also further reinforce Veracyte’s commitment to evidence generation that supports the Decipher Prostate test’s ‘Level 1B’ evidence status—the highest among commercially available gene expression tests—in the most recent NCCN [National Comprehensive Cancer Network] Guidelines for prostate cancer.”

Overall, the phase 2 ENACT trial enrolled 227 patients with low- to intermediate-risk prostate cancer to compare the safety and efficacy of enzalutamide monotherapy plus AS vs AS alone. Patients were randomly assigned 1:1 to receive 160 mg orally once daily enzalutamide or to continued AS for 1 year.

For the study, the investigators conducted transcriptional analyses on biopsies from baseline, year 1, and year 2. The 3 gene expression signatures were evaluated in samples collected at screening (analytic cohort) and those collected at screening and at any time during surveillance (expanded cohort).

Data from the pre-planned biomarker analysis showed that higher scores on the Decipher genomic classifier were associated with disease progression among patients in the expanded cohort (MVA HR, 1.17; 95% CI per 10% increase in score, 1.01 to 1.35; P = .04) and those in the AS arm of the expanded cohort (MVA HR, 1.23; 95% CI per 0.1, 1.05 to 1.44; P = .01)after adjusting for baseline and clinical risk factors. There was a non-significant association between Decipher score and progression among patients who received enzalutamide (MVA HR, 1.50; 95% CI per 0.1, 0.91 to 2.48; P = .11).

Neither AR-A nor PAM50 were associated with disease progression or the incidence of negative biopsy at 1 year among patients in the AS arm.

Among patients in the treatment arm, higher Decipher score was associated with a greater positive treatment effect from enzalutamide, as determined by the time to secondary rise in prostate-specific antigen level of greater than 25% above baseline (P = .03).

Further, among patients who received treatment with enzalutamide, higher AR-A scores were associated with greater odds of a negative biopsy incidence at year 2 (P = .04), as well as those who had tumors of the luminal subtype (P = .01). Specifically, among patients treated with enzalutamide, 50% of those who had luminal tumors had a negative biopsy at year 2, compared with 9% of those with basal tumors.

The authors concluded,¹ “In conclusion, this preplanned ENACT trial biomarker analysis demonstrates the value of the Decipher score, AR-A score, and PAM50 genomic classifiers in identifying patients undergoing AS who are most likely to benefit from enzalutamide treatment. Future studies will aim to validate the utility of these genomic classifiers in a larger patient cohort.”

References

1. Ross AE, Iwata KK, Elsouda D, et al. Transcriptome-based prognostic and predictive biomarker analysis of ENACT: A randomized controlled trial of enzalutamide in men undergoing active surveillance. JCO Precis Oncol. 2024:8:e2300603. doi:10.1200/PO.23.00603

2. New study shows Veracyte’s Decipher Prostate Test is prognostic for prostate cancer progression among patients undergoing active surveillance. News release. Veracyte, Inc. Published online and accessed April 22, 2024. https://investor.veracyte.com/news-releases/news-release-details/new-study-shows-veracytes-decipher-prostate-test-prognostic