Don’t gimme the loot.

Top Line: Treatment for metastatic castration resistant prostate cancer (mCRPC) largely boils down to: are you going to go with additional androgen axis blockade (e.g., enzalutamide or abiraterone) or cytotoxic chemo (e.g., docetaxel)?
The Study: Based on the trial data, your decision could be swayed by the extent of metastatic disease—typically low volume, non-visceral versus high volume or visceral. You could also factor in the emerging biomarker androgen receptor splice variant 7 (AR-V7) that contributes to androgen blockade resistance. In the PROPHECY trial men with mCRPC starting abiraterone or enzalutamide were prospectively tested for AR-V7 in circulating tumor cells, with complicated inclusion criteria designed to enrich the population for this test. Two slightly different assays were used on all patients. Using the mRNA-based Johns Hopkins assay, 24% of men were AR-V7(+) while just 9% were positive using the Epic protein-based assay with an 82% agreement between tests. Regardless of test, the outcomes were fairly consistent. Men with AR-V7 had very little benefit from enzalutamide or abiraterone with a median progression-free and overall survival of only 3 and 10 months, respectively, compared to 6 and 25 months without AR-V7.
Bottom Line: Men with AR-V7(+) circulating tumor cells from mCRPC derive little clinical benefit with the addition of enzalutamide or abiraterone to ADT. Where do we order? | Armstrong, J Clin Oncol 2019


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