Data from a major clinical trial from the Alliance for Clinical Trials in Oncology has uncovered a genetic factor that may inform how to optimize the dosing of abiraterone, a widely used hormonal treatment for advanced prostate cancer. Published by Norton et al in Clinical and Translational Science, this secondary analysis of Alliance A032201 could lead to more personalized treatments for patients.
“This study is the first to show how an individual’s genetics can impact how abiraterone is metabolized. These findings could lead to optimized dosing strategies in the future, rather than giving the same dose of the drug to everyone, as we do now,” said author Michael Morris, MD, the Steven A. Greenberg Chair in Prostate Cancer Research at Memorial Sloan Kettering Cancer Center.
The Alliance A031201 trial was a large phase III study conducted by the Alliance, a national research network supported by the National Cancer Institute. The trial enrolled 1,311 men with metastatic castration-resistant prostate cancer and randomly assigned them to receive the hormonal therapy enzalutamide either alone or in combination with abiraterone.
As part of this study, researchers collected genetic data and measured drug levels in the blood to see if certain genes influence how these agents are metabolized. That genomic data was analyzed for this current research.
“We discovered that men who carry a specific version of the gene SULT2A1 clear abiraterone from their bodies more slowly,” said lead author Nadine Norton, PhD, Associate Professor of Cancer Biology for the Mayo Clinic in Jacksonville, Florida. “This means the drug stays in the system longer, which could affect how well it works and whether side effects occur.”
Interestingly, the study did not find any similar genetic effect for enzalutamide, suggesting that this discovery is unique to abiraterone. This finding opens the door to more personalized care. In the future, doctors may be able to test for this gene variant (found in about 15% of people of European descent) and adjust abiraterone doses to make treatment safer and more effective.
“The initial trial gave us the data to make this discovery,” added Dr. Morris, who was study chair of the original Alliance study. “This new genetic finding is an important step toward precision medicine in prostate cancer care.”
DISCLOSURE: This research was supported by the grants from National Cancer Institute, Astellas Pharma Inc, and Pfizer. For full disclosures of the study authors, visit ascpt.onlinelibrary.wiley.com.
