Exploring the role of RB and AR in a phase II randomized multicenter trial of abiraterone acetate with or without cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC).

TPS5093Background: Retinoblastoma (RB) loss of function has been identified as a process by which castration-resistant tumors develop. Up to 60% of CRPC tumors show loss of RB function. This can drive the transition to castration resistance in human xenograft models. The androgen receptor (AR) appears to be under stringent RB control; RB loss results in AR deregulation and bypass of androgen deprivation therapy. Tumors lacking RB are compromised for DNA damage checkpoints that allow for repair after genomic insult. Thus,tumors devoid of RB function are hypersensitive to chemotherapy. These findings support the hypothesis that RB status can guide treatment with specific chemotherapies and improve disease outcome. RB status may be a potential biomarker for pts who fail AR-directed drugs such as abiraterone (AA). While docetaxel is the standard first line chemotherapy for mCRPC, cabazitaxel (CBZ) is a more potent microtubule inhibitor. This trial will determine the effect of AA followed by CBZ upon disease p...