First I totally agree with gratitude to all participants in clinical trials. I remember when Sonny and a few other guys I have associated with that were on this trial. Of course all I could do is cheer them on because the purpose of any clinical trial is to answer a question and we had not had these questions answered yet with TAK700.
I brief history of TAK700 in prostate cancer. Dating years back before even we had docetaxel (TAX327 Trial in 2004) we had several potential drugs in regular use. One such drug was Ketocanazole, or Keto for short. Keto worked to some degree by inhibiting the enzymes CYP17,20. The down side of Keto is that it destroyed livers. Researchers looked for better ways to attack this pathway and eventually in 2009 abiraterone acetate cleared with expedited release as a well working Cyp17, 20 inhibitor. It extended lived. On the down side of the drug is the requirement for a corticosteroid. Prednisone. TAK700 was being researched in Japan and could be seen as an alternative to abiraterone. Here is a breakdown of this research:https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3047603/
TAK700 had failed in demonstrating improved survival in mCRPC patients in previous trials. It was questionable if is would work in the mHSPC setting. Enter S1216. However after these trials all failed, I see a likely end to TAK700 after S1216 for use in prostate cancer.
The STAMPEDE trial showed that abiraterone worked in the mHSPC setting but it came with the need for a steroid. If TAK700 could show a 25% improvement in S1216 in OS in S1216 it would be a reasonable alternative to Zytiga. It did not do so. Thus it was not considered a success. As it is, it was still a great trial that gave us great information. That's what a long and drawn out trial with good design can do even if the experimental drug does not make its endpoints.
Considering the ties between abiraterone and TAK700 both being CYP17,20 attack mechanisms, It is not likely that they could be used together to improve the results. This is one of the Exclusion Criteria of S1216 was:
"Prior or concurrent therapy with ketoconazole, aminoglutethimide or abiraterone acetate, or enzalutamide (MDV3100)."
Simply put these AR drugs would contaminated our trial. And in the end they were disallowed unless progression indicated allowing their use.
Post Edited (Tony Crispino) : 7/4/2021 4:35:32 PM (GMT-6)