PROPHECY Study: Phenotypes Associated with Poorer Survival in mCRPC Treated with Abiraterone or Enzalutamide

A study found an independent relationship between high chromosomal instability (CIN) and neuroendocrine (NE) circulating tumor cells (CTC) phenotype and poorer survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide. The results were published in Clinical Cancer Research.

In the PROPHECY trial, researchers assessed men with mCRPC starting abiraterone or enzalutamide. As a secondary outcome, they analyzed Epic CTC CIN and NE phenotypes before abiraterone or enzalutamide and at progression. The researchers implemented a proportional hazards (PH) model to determine the relationships between CIN and NE and progression-free survival and overall survival (OS), adjusting for CTC number, AR-V7, prior therapy, and clinical risk score.

A total of 118 patients with mCRPC were enrolled in the study, and 107 had evaluable outcomes on the Epic platform. The researchers reported that 36.4% of men were CIN positive, and 8.4% were NE positive. Independent associations were observed between CIN and NE and poorer OS when treated with abiraterone or enzalutamide, with respective hazard ratios (HRs) of 2.2 (95% confidence interval [CI], 1.2-4.0) and 3.8 (95% CI, 1.2-12.3). When implementing the PH model in a separate dataset of patients from Memorial Sloan Kettering Cancer Center, NE positivity was still associated with poorer OS (HR=5.7; 95% CI, 2.6-12.7).

“A high CIN and NE CTC phenotype is independently associated with worse survival in men with mCRPC treated with abiraterone/enzalutamide, warranting further prospective controlled predictive studies to inform treatment decisions,” the study authors concluded.