X then Z makes most sense to me based on their respective side effect and efficacy profile. That's going to be even more the case with earlier stage disease.
I'd guess that the drugs are similar enough that you won't buy all that much with successive use - perhaps more with X after Z than vice versa, but in neither case enough to get excited about.
Ultimately I think we will see some sort of combination therapy in patients that fail these drugs - perhaps something involving the PI3K/AKT pathway, as this has been shown to have crosstalk with the AR pathway. Or add an HSP90 drug perhaps.
What I'm most anxious to see is how very early-stage patients respond to these drugs, for example in a neoadjuvant setting prior to surgery for localized disease. I'm of the "take your best shot upfront" school - using a sub-optimal treatment and waiting for resistance to develop before moving on to the better drug makes no sense to me.
Peter
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