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Exelixis, Inc. Message Board

  • wilderguide wilderguide Oct 4, 2013 11:15 AM Flag

    Biomarker Prognostics in mCRPC

    $$$$
    Onclive 10/3/13... On Dr Scher's ECC presentation.
    GLTA

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    • Thanks Wild...24 month survival seems outstanding. How might this abiraterone acetate plus prednisone result influence the cabo-abiraterone acetate or prednisone trials?

      • 2 Replies to kcbs2
      • $$$$
        " How might this abiraterone acetate plus prednisone result influence the cabo-abiraterone acetate or prednisone trials?"
        Took me a bit to find, but knew this question had been asked before...
        Kcbs, when you asked this question back in Oct, I'd no clue what the future would hold.
        However, I now believe the designated P2 Cabo/Abi trial population size says it all, as n=280.
        This smells very optimistic to me, and a future expansion cohort wouldn't surprise me. When we get some reporting on these Abi combination trials, I think it a fair guess that the uro-oncological research world will be in full attendance. The potential for Cabo/Abi synergy has been hyped a bit, but not without sound clinical rationale. Of particular interest to me is the 20mg every other day cohort. In a perfect world, the combined effect of hormone manipulaton and MET/VEGF/RETi might even eliminate the need for concomitant prednisone. Imagine a future in which a 90% probability of bony mets is no longer the statistic norm for CRPC, and is replaced by a percentage closer to 30%-ish.. There's a great "what-if" for you..
        What's that worth?
        GLTA

      • $$$$
        This is the important question, of course, but I would encourage you to consider the relevance of the biomarker survey before we begin to discuss the drug combo. We know that Cabo displays a clinically reliable reduction in 12-week CTC counts that meets the bioassay criteria. We also know that Cabo moderates elevated LDH in this same 12-week timeline. These markers have been associated with improved survival...as have been Cabo's notable pain reduction, bone scan response, and diminished narcotic intervention for pain relief. Responsibly tying all these markers together into a predictive mechanism that satisfies regulatory acknowledgement may not happen soon enough to help get Cabo approved in the prostate space, but the medical community is quickly gaining momentum in it's acceptance of the emerging pattern of concurring markers that certainly appears to suggest improved OS, if only in mCRPC. Going forward, I will encourage the opinion that each indication will be different, as may each stage of disease progression.

        All this certainly lends an air of intrigue to the Cabo/Abi combo...but the fact is - we haven't been dealt enough info to make much informed discussion except to say early results are encouraging. This could hold up thru P1 results, or that early synergy could fizzle or be bested by the changing landscape of PC treatment. There is simply a lot that we won't know till results are in...
        But the results to date are very striking, and I am more optimistic with each new clinical reassurance.
        Doc Scher wouldn't waste his time developing such a biosurvey in mCRPC unless he saw promise in it, and it is very encouraging that many of the same markers that were noted in the Abi trial apply to Cabo as well. Blast or bust - this is going to be great fun to watch...
        Hopefully, we'll all make a buck or two...
        GLTA

 
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