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iwfal

05/23/12 12:38 AM

#142408 RE: NP1986 #142404

I think subgroup analyses in some of the anti-EGFR antibody trials have shown that KRAS mutant patients actually did worse in terms of PFS than the control group. I can't recall any specific trials though.



Correct. Although of all the examples I cited it has the weakest dichotomy it nonetheless repeats across many different trials and combos in CRC. Each individual p value nothing definitive (except combo with FOLFOX) but in aggregate very definitive.

I think part of this may be due to do compensatory mechanisms, i.e. when you inhibit one pathway, you activate another one.



Agreed - but it is an interesting and non-intuitive effect. Damaging the OS I can understand (via toxicity to patient), but accelerated tumor growth commonly occurring across the meta-class is just very counter intuitive to me.

Or it could just be statistical noise.



No, I was moderately careful to pick only fairly definitive examples. That said, it is may be a little bit hyperbolic to say that more typical than atypical since even in these drugs I didn't check to see how many indications it happened in. E.g. Does Erbitux have similar characteristics in Head and Neck cancers?