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Genomic testing has significant prognostic utility in optimizing the use of apalutamide (Erleada) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to a retrospective analysis of the phase 3 SPARTAN trial published in JAMA oncology.1,2
In the analysis, the Decipher Prostate genomic classifier (GC), a 22-gene microarray-based assay, identified potential biomarkers of response to apalutamide in this setting. Specifically, patients whose GC test results showed them as having high-risk disease and/or the luminal disease subtype derived the greatest benefit from receiving apalutamide.
“These findings are an important addition to our growing understanding about how best to manage patients across the long trajectory of prostate cancer,” Felix Y. Feng, MD, professor of Radiation Oncology, Urology, and Medicine, and vice chair for Translational Research, Department of Radiation Oncology at the University of California, San Francisco, who is a SPARTAN study investigator and the paper’s primary author, stated in a press release. “They suggest that genomic testing provides useful information to guide treatment decisions that may improve outcomes among men with locally advanced disease, a population for which we’ve previously lacked genomic biomarkers.”
The phase 3 SPARTAN trial (NCT01946204) randomized 1207 patients with nonmetastatic CRPC in a 2:1 ratio to apalutamide or placebo plus ongoing androgen-deprivation therapy (ADT). In the overall study population, treatment with apalutamide plus ADT significantly improved metastasis-free survival (MFS) versus placebo plus ADT (median MFS, 40.5 vs 16.2 months; 0.28; P <.001). Median overall survival (OS) was also significantly improved with apalutamide (73.9 vs 59.9 months; HR, 0.78; P = .016).3 Based on results from the SPARTAN trial, the FDA approved apalutamide in 2018 for use in this setting.
The retrospective analysis assessed gene expression data from archived tumors samples from 233 patients. The samples were collected at radical prostatectomy or during diagnostic biopsies. The median patient age was 73 years (range, 49-91). Using the Decipher Prostate GC, patients were stratified into high-risk and low-risk groups for developing metastases. The Prostate GC was also used to stratify patients into basal and luminal subtypes.
Overall, 116 of 233 patients had high GC risk scores. The analysis found that while all patients benefited from apalutamide, the greatest benefit occurred in these patients with high GC risk scores. In this group, the HR for MFS was 0.21 (P <.001) and the HR for OS was 0.52 (P = .03).
Across the 233 patients, 152 had the basal molecular subtype and 81 had the luminal subtype. The analysis showed that among the apalutamide-treated population, patients with the luminal subtype had significantly longer MFS compared with those with the basal subtype (HR, 0.40; P = .03).
“The molecular signatures examined in this study appear to have prognostic utility and can be useful in clinical decision-making regarding treatment intensification in patients with nonmetastatic castration-resistant prostate cancer at high risk for metastasis; larger studies are warranted for validation of these findings,” Feng et al wrote in the conclusion of their manuscript.
1. New Data Published in JAMA Oncology Demonstrate Prognostic Utility of Veracyte’s Decipher Prostate Genomic Classifier in Locally Advanced Prostate Cancer. Published online June 14, 2021. Accessed June 14, 2021. https://bwnews.pr/3gqmiJC.
2. Feng FY, Thomas S, Saad F, et al. Association of molecular subtypes with differential outcome to apalutamide treatment in nonmetastatic castration-resistant prostate cancer [published online ahead of print June 3, 2021]. JAMA Oncol. 2021. doi: 10.1001/jamaoncol.2021.1463.
3. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79(1):150-158. doi:10.1016/j.eururo.2020.08.011