Since it FDA approval in 2004, docetaxel (a taxane based chemotherapy) has been the standard first-line chemotherapy for men with metastatic prostate cancer (mCRPC).
Other than the trial of Provenge all the successful phase III trials conducted in mCRPC focused on men experiencing cancer progression after first-line docetaxel chemotherapy. The implication is that improving the outcome of these men was the most critical unmet need facing men with prostate cancer. Additionally, men at this stage provided an opportunity to demonstrate an overall survival improvement more rapidly over a shorter time frame.
Since the approval of docetaxel four different drugs have been shown to provide an overall survival benefit on top of other clinical improvements for men whose disease progressed after their having had docetaxel: cabazitaxel (Jevtana), abiraterone (Zytiga), radium-223 (Xofigo), and enzalutamide (Xtandi).
Prior to 2010 the best standard of care after docetaxel failure was considered another round of docetaxel a few months after the initial failure (there is no evidence that this second round provided any survival advantage). Then mitoxantrone with prednisone was used which only provided palliative benefit (no survival advantage).
Now, given the fact that they supply a survival advantage, it is clear that these other, new drugs should be the next treatment steps after docetaxel failure.
Cabazitaxel (Jevtana), which is a newly approved “second-generation” taxane was shown to improve overall survival when added to prednisone compared with mitoxantrone plus prednisone in the TROPIC trial (hazard ratio