Outcome-adaptive randomized platform trial of androgen receptor pathway inhibitors and taxanes in metastatic castration-resistant prostate cancer

The multinational Prostate Biomarkers (ProBio) trial randomized patients with metastatic castration-resitant prostate cancer (mCRPC) after prospective circulating tumor DNA and germline DNA analysis to androgen receptors pathway inhibitors (ARPIs), taxanes, or physician’s choice (PC). Primary endpoint was time to no longer clinically benefitting (NLCB). Among biomarker-unselected patients, NLCB and overall survival were better with ARPIs than with taxanes or PC. Biomarker signature findings suggest that the largest increase in time to NLCB with ARPIs versus taxanes was observed in AR-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. The authors conclude that ARPIs outperform taxanes in mCRPC patients with specific alterations in circulating tumor DNA.