Methylation-Based Tumor Fraction (ctDNA) Beats PSA for Predicting Rucaparib Outcomes in BRCA deficient mCRPC

In TRITON2 (NCT02952534), a Phase 2 study of rucaparib (an approved PARP inhibitor) in BRCA mutation deficient (germline and/or somatic) metastatic castration-resistant prostate cancer, a lower baseline plasma tumor fraction (TF) derived from hyper-methylated DNA median = 25%; n = 230) predicted improved radiographic PFS (HR 0.54) and overall survival (HR 0.42) compared to patients with baseline TF > median. In contrast, baseline PSA correlated only with OS (HR 0.52) and not PFS (HR 0.71). TF correlated modestly with Gleason score (p = 0.012) but was largely independent of PSA (R² = 0.09).