A novel genetic test shows promise in predicting which patients with metastatic prostate cancer will experience a survival advantage from docetaxel treatment. Findings from the Phase III STAMPEDE trial, presented at the ESMO 2024 Congress, indicate that the Decipher Prostate Genomic Classifier can serve as a prognostic tool for clinical outcomes and predict the benefits of docetaxel in this patient population.
Deciphering Docetaxel's Impact
While adding docetaxel to androgen deprivation therapy (ADT) has been shown to improve survival in some men with metastatic prostate cancer, not all patients benefit. "Understanding who will benefit from docetaxel is a major medical challenge," explained Dr. Emily Grist of the UCL Cancer Institute at University College London. The STAMPEDE trials included 3,909 randomized prostate cancer patients and 377 overlapping control patients. Researchers analyzed data for 1,523 patients with advanced or metastatic prostate cancer who were followed in the STAMPEDE trial for a median of 14 years.
The study linked tumor multi-gene expression signatures with 14-year overall survival data, utilizing clinical-grade transcriptome-wide gene expression profiling of prostate tumors with prospectively acquired clinical data. Metastatic disease was subdivided into low (52%) and high volume (41%).
Prognostic Power of Decipher
The study revealed that higher Decipher Prostate test scores were associated with an increased risk of death in both groups. Comparing ADT versus ADT plus abiraterone, the hazard ratio (HR) was 0.44 in Decipher high patients and 0.70 in Decipher lower patients. However, biomarker treatment interaction was not statistically significant nor clinically relevant.
Importantly, among the 832 patients with metastatic disease, only those with higher Decipher Prostate scores experienced a significant survival benefit from adding docetaxel to ADT. These patients saw a 36% reduction in the risk of death with the addition of docetaxel compared to those with lower Decipher scores (HR: 0.96), who did not benefit significantly. Docetaxel was beneficial in patients with higher Decipher Prostate scores regardless of whether they had high-volume or low-volume prostate cancer.
Clinical Implications
"High Decipher score predicts improved survival with docetaxel in addition to ADT in directly randomized patients," Dr. Grist stated. "Patients with synchronous metastatic prostate cancer and Decipher low tumors do not derive benefit from docetaxel in addition to ADT. Decipher classifier is the first molecular biomarker to predict docetaxel sensitivity in advanced prostate cancer and is independent of metastatic volume."
According to STAMPEDE trial co-investigator Dr. Gerhardt Attard, the findings are significant because "they show that the Decipher Prostate test can help clinicians better distinguish patients with metastatic prostate cancer who receive the greatest benefit from docetaxel from those who don't and may therefore avoid unnecessary toxicity."
About the Decipher Prostate Test
The Decipher Prostate Genomic Classifier is a 22-gene test that uses RNA whole-transcriptome analysis and machine learning to inform treatment decisions for prostate cancer patients. The test, performed on biopsy or surgically resected samples, provides an accurate risk assessment of developing metastasis with standard treatment. The new findings may expand the use of the Decipher Prostate test to patients with metastatic disease. The Decipher Prostate test will be offered to patients with metastatic prostate cancer in early 2025 after its anticipated reimbursement by Medicare.
