On May 25, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that new data to be shared at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrate the ability of the company’s Decipher Genomics Resource for Intelligent Discovery (GRID) database to enable novel molecular insights into prostate cancer (Press release, Veracyte, MAY 25, 2023, View Source [SID1234632083]). The findings, from three separate studies, may ultimately help inform more personalized treatment for patients with prostate cancer.
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"The Decipher GRID-based data that will be shared at this year’s ASCO (Free ASCO Whitepaper) meeting help advance our collective understanding of how to use transcriptomic information in the treatment of prostate cancer," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "This includes new insights into specific molecular profiles that may predict individual tumors’ response to treatment. The findings also shed light on transcriptomic differences underlying various types of prostate cancer and the changes that occur over the course of the disease as well as in response to therapy."
A poster presentation on June 3 (Abstract #5094; Poster #188) will highlight findings from an analysis of the Phase 3 randomized clinical trial NRG/RTOG 0521, which examined the role of molecular subtyping in prediction of response to docetaxel chemotherapy among patients with high-risk prostate cancer who were treated with radiation and androgen deprivation therapy (ADT). Researchers classified 183 pre-treatment biopsy samples into basal or luminal subtypes using a Decipher GRID-derived, 215-gene expression signature. This signature was previously shown to classify prostate cancer into four molecular subtypes: luminal differentiated, luminal proliferating, basal immune, and basal neuroendocrine-like. Patients in this trial were followed for a median of 9.9 years.
Results suggest that patients with high-risk localized prostate cancer that is classified as a luminal proliferating (LP) subtype derive greater benefit from the addition of docetaxel to RT and ADT than those with non-LP subtypes. Differences in restricted mean survival times (RMST), a measure of the average survival time gained or lost by receiving chemotherapy, were examined at 5 and 10 years. Among patients who received docetaxel, at 5 years, LP subtype patients on average gained 3.8 months in overall survival and 13.7 months at 10 years. In contrast, patients with non-LP subtype had more modest differences in RMST with the addition of docetaxel (-0.2 and 2.5 months at 5 and 10 years, respectively).
"The findings from this study are consistent with those from a similar analysis of the Phase 3 randomized, controlled CHAARTED trial, which demonstrated a differential response to docetaxel chemotherapy among patients with hormone-sensitive metastatic disease and LP subtype," said Phuoc T. Tran, M.D., Ph.D., professor and vice chair for research of Radiation Oncology at the University of Maryland School of Medicine and senior author of the new study. "These new findings further suggest that prospective validation of basal-luminal subtyping for patients with high-risk and metastatic disease may enable more effective, earlier use of docetaxel in appropriate patients."
A second poster presentation on June 3 (Abstract #5026; Poster #120) will summarize findings from an analysis of transcriptomic changes that occur over time in patients with low- or intermediate-risk prostate cancer undergoing active surveillance (AS) and those treated for one year with enzalutamide in the ENACT trial.
Researchers used the Decipher GRID platform to perform gene-expression profiling on tumor samples from 131 ENACT participants collected at pre-specified time points (screening, 12 months and 24 months). Analysis with pre-defined molecular signatures on the GRID platform showed that after treatment with enzalutamide for one year, androgen receptor signaling and immune-suppressor genomic signatures were downregulated, while activated immune and basal-like biology markers were upregulated. Additionally, one year after stopping enzalutamide treatment, most signatures returned, or nearly returned, to baseline levels. Researchers also identified changes in genomic signature activity in the AS arm from screening to the 12- and 24-month follow-up time points.
"This analysis provides valuable insights into the progression of early prostate cancer among patients undergoing active surveillance and those treated with enzalutamide," said Ashley Ross, M.D., Ph.D., associate professor of Urology, Northwestern University Feinberg School of Medicine and lead author on the abstract. "These findings could ultimately help inform treatment considerations for patients with low- or intermediate-risk prostate cancer, as well as potential new immunotherapy strategies."
In the third study (#e17083), researchers used the Decipher GRID database to identify differences in transcriptomic profiles between castration-sensitive prostate cancers that became metastatic within six months of primary cancer diagnosis (synchronous mCSPC) and those that became metastatic after six months of primary cancer diagnosis (metachronous mCSPC). They then assessed how these differences impacted response to therapy. The findings suggest a biological difference between metastatic timing, which could potentially help inform treatment decisions for patients with mCSPC.
The Decipher GRID database includes more than 100,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its research partners to help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis to physicians who have ordered the Decipher Prostate Genomic Classifier.