I think we have to keep in mind here that the "confounding" effect of these treatments is going to occur, in this trial, in a post-chemo context. It may be the case that they do even more for OS pre-chemo, but none of the pts in SYNERGY will have gotten either xtandi or zytiga pre-chemo.
So I think a median of 24 or 25 is in play for the control arm in SYNERGY, but anything above that would a really big surprise. VENICE and READY are good proxies for little xtandi or zytiga add-on, and the pre-chemo results for their usage showed a 4 to 5 month add-on.
" but none of the pts in SYNERGY will have gotten either xtandi or zytiga pre-chemo."
That's mostly correct but not 100% (at least for zytiga). If you look at the zytiga sales, already some of the sales were coming from prechemo space even before the prechemo trial got unblinded. If I were TEVA, I would have encouraged the doctors to suggest the trial to these patients.
Incidentally, If I were TEVA, I would have guided the doctors towards the patients who already used ketoconazole.
These are not unethical behaviors as I believe in most cases these work for the best interest of the patients.