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Exelixis, Inc. Message Board

  • hbomb57108 hbomb57108 Feb 17, 2013 12:49 PM Flag

    40% of clinicians are probably ok with off-label usage of Cabo with reimbursement despite no OS data

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    • "Any idea what these guys are referring to...?? This format exactly matches a bunch of twitters coming out of ASCO GU on Saturday, but I can't match it up to any particular event. Might be meaningless if it were a show of hands at a stoned-out Led Zeppelin concert...but it sure makes me wonder who was in that audience, and who would conduct such a survey. Still looking..."


      This is referring to audience at this event

      Friday, February 15, 2013, Orlando, FL, 7:00 PM – 9:00 PM (Eastern Time)
      Current Clinical Controversies and Promising Therapeutic Strategies in Advanced Prostate Cancer: A Live Clinical Investigator Think Tank

      What is known about the benefits and risks of cabozantinib? What is the explanation for the effects on bone metastases, particularly in terms of improving bone scans? What ongoing trials include this agent, and when are results expected? "

      I wouldn't get too hung up on that 40% number as I believe that is assuming off-label usage, and no statsig OS data to date.

      • 1 Reply to hbomb57108
      • I'd like to believe Cabo would have substantial off label usage, but I think Alpharadin might scoop it for the time being. Alpharadin has hardly any side effects, and I imagine any that do crop up would take longer than most targeted patients' expected time to live. A recent interview w/ Voglezang on Onclive has him singing praises of Radium-223 as being one of the two or three drugs (along w/ DHT suppressor Abirateron and AR signaling blocker Enzalutamide) that he would bring to a desert island for patients w/ prostate cancer. He is just one doctor, albeit one who knows both compounds; I'm sure there might be some who prefer Cabo, but I think most will prefer Alpharadin for its low AE profile, and upcoming FDA approval will make it easier to seek reimbursement and make confident prescriptions as well.

        That said, Alpharadin is probably not doing anything for the soft-tissue component of prostate cancer where the metastases originate and probably not much for soft-tissue metastases. Dosing regimens for Cabo have yet to be fully established but preliminary results seem to indicate that lower doses ~60-40 mg are active and well tolerated. What's more, Cabo might directly play into synergies w/ other inhibitors by blocking cross-talk in signaling mechanisms, whereas Alpharadin is a relatively brute method in comparison. Alpharadin will be first to treat bone metastises, but the Cabo mechanism sounds like it could easily stack on top of it and after any of the other AR related treatments available.

        I think Cabo's day in the sun will come but probably not until 2014 or later, and most likely in conjunction with other treatments. Its mechanism seems to be most helpful only after blocking AR signaling fails, so the early stage market still belongs to Enzalutamide and Abiraterone, bu I could see it being introduced earlier as it's probably hard to tell when Cancer makes its transition to c-Met expression from androgen dependence.

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