Replies to post #142414 on Biotech Values

[iwfal]

But given the drug is being given on top of active therapy, it is still unclear whether the worse outcome may not be the result of the additional tox issues causing more morbidity and/or FOLFIRI dose reductions and interruptions. To try to answer that question, you'd have to compare dose intensity and side effects in the two arms.

Agreed that, as NP pointed out as well, this is a possibility and has to be more explicitly ruled out. I have already done some of this filtering - e.g. in a previous post I note that the harm done to pfs in Met- patients in MetMab plus Tarceva is greater than the effect you'd expect if you just provided no Tarceva at all ever in that arm. I.e. it isn't just a discontinuation issue. (Obviously it could be a combo of this effect and tox so bad it is killing some patients - but again this seems unlikely.)

Other notes are that I believe, anecdotally, that traditional chemo does not show this subgroup pfs harm to anywhere near the degree it often pops up in the more targetted kinase actors. But again, I'd need to do more research to make it less anecdotal.

[iwfal]

But given the drug is being given on top of active therapy, it is still unclear whether the worse outcome may not be the result of the additional tox issues causing more morbidity and/or FOLFIRI dose reductions and interruptions.

Followup post - while I agree it could be tough in some instances to 'prove' that the worse pfs in the treated arm is NOT due to extra tox etc, there are other instances where it is less difficult (e.g. MetMab's extreme dichotomy), and in yet others it is clear cut that these kinase actor treatments do speed growth of some tumors:

Zelboraf is the most famous (hugely accelerating squamous cell cancer) - but some other kinase actor drugs have a similar problem listed on their label, albeit with much less frequency than Z (can't remember which one(s) right now - but I know I bumped into it sometime in the last several months).

Note that I agree in advance that Z is an oddity in the sense that it isn't even targeting wild type gene - so how is it having an effect anywhere but the mutant BRAF? (I'd love to know the MOA for this causing of squamous cell cancer). But, as I said, Z is not alone in this kind of effect - just the most extreme known.