Phase 2 randomized cross-over trial of abiraterone + prednisone (ABI+P) vs enzalutamide (ENZ) for patients (pts) with metastatic castration resistant prostate cancer (mCPRC): Results for 2nd-line therapy.

5015Background: ABI+P and ENZ have similar efficacy for 1st-line treatment of mCRPC but cross-resistance confounds treatment with the alternate agent at progression. The optimal sequencing has not been prospectively investigated and predictive biomarkers are needed. Methods: A multi-centre trial of ABI+P followed by ENZ at PSA progression (arm A) vs ENZ followed by ABI+P (arm B). Primary endpoints were PSA decline > 50% (PSA50) on 2nd-line therapy and time to 2nd PSA progression (TT2P) (from start of 1st-line). Deep-targeted sequencing of serial samples of circulating tumour DNA (ctDNA) was performed. Results: 202 pts (101/ arm) were accrued with median follow-up 22.3 months (m). 65 pts from arm A and 71 from arm B crossed-over to 2nd-line treatment and 30 pts (15/arm) stopped treatment without cross-over. Baseline characteristics at time of 2nd-line therapy were balanced: median age 75 (range 50-93), PSA 14.5 (6.6-62.1), alkaline phosphatase > upper limit of normal (ULN) in 39% of pts and bone/liver meta...