November 11 2021
NRG-GU010: Parallel Phase III Randomized Trials of Genomic-risk Stratified Unfavorable Intermediate Risk Prostate Cancer: De-Intensification and Intensification Clinical Trial Evaluation (GUIDANCE)
Up to half of men succumbing to prostate cancer are initially diagnosed with localized disease. Preventing under-treatment in such men while minimizing over-treatment of men with lower risk disease depends upon risk models, which may be improved by promising new gene risk scores like Decipher. In the large population of men with traditionally defined unfavorable intermediate risk prostate cancer, the current standard of care is radiotherapy with 6 months of androgen deprivation therapy (ADT). It is hypothesized that accounting for Decipher gene risk within this patient population could help determine which patients may benefit from a higher intensity treatment versus a lower intensity treatment.
“NRG-GU010 was designed to determine if radiotherapy alone can have the same impact as the standard of care radiotherapy and androgen deprivation therapy for people with a low gene risk score. Additionally, this trial addresses the question whether adding additional hormone therapy (darolutamide) to treat people with high gene risk scores can increase the amount of time before their cancer returns or spreads,” stated Neil Desai, MD, MHS of the University of Texas Southwestern Medical Center and the Co-Principal Investigator of the NRG-GU010 trial.
NRG-GU010 contains two parallel studies. The first study (de-intensification study) assesses unfavorable intermediate risk prostate cancer with a Decipher score below 0.40 (lower gene risk score). Patients in this study would be stratified by co-morbidity burden and radiotherapy regimen intensity, then randomized to receive either radiotherapy alone or radiotherapy with 6 months of ADT. The second study (intensification study) is for patients with a Decipher score of 0.40 or greater (higher gene risk score). Patients in this study would be stratified by their Decipher score (0.40-0.60 vs. greater than 0.60), co-morbidity burden and radiotherapy regimen intensity, then randomized to receive either radiotherapy with 6 months of ADT or radiotherapy with 6 months of ADT and 6 months of darolutamide. Darolutamide is a newer anti-androgen with much greater ability to suppress prostate cancer signaling and demonstrated survival improvement in men with “ADT resistant” disease that has not spread beyond the pelvis.
“It is important to alter our practices and treatment to meet specific patient needs. If we are able to isolate genomic factors within the disease type, we should be personalizing treatment plans based on the best option for each disease subgroup,” said Alejandro Berlin, MD, MSc of the University Health Network Princess Margaret Cancer Centre and Co-Principal Investigator of the NRG-GU010 trial.
The primary objective of the de-intensification study is to determine whether men with a lower Decipher genomic risk score treated with radiotherapy alone experience a non-inferior rate of distant metastasis when compared to patients who receive radiotherapy and ADT. The primary objective of the intensification study is to determine whether men with a higher Decipher genomic risk score treated with radiotherapy, ADT, and the additional darolutamide have a superior metastasis-free survival when compared to patients receiving radiotherapy and ADT. Secondary objectives include comparing overall survival, time to PSA failure, cumulative incidence of locoregional failure, cumulative incidence of distant metastasis, prostate-specific mortality, sexual and hormonal quality of life, fatigue, and cognition between studies and treatment arms.
Radiotherapy regimens are very flexible with a broad allowance of NCCN recognized external beam (i.e. conventional fractionation, moderate hypofractionation, ultra-hypofractionation SBRT, use of ‘micro’-boost) and brachytherapy (high dose rate or low dose rate) approaches.
Decipher gene risk scores can be obtained without charge through the study, or patients can enter the study with already commercially obtained scores. Darolutamide is provided for patients assigned to its use by the trial.
Learn more about this trial on ClinicalTrials.gov
Protocol documents and materials are located on the CTSU website.