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Exelixis, Inc. Message Board

  • wildbiftek wildbiftek Oct 23, 2013 9:59 AM Flag

    TKI Switch Shows Promise in Thyroid Cancer

    "Dadu and colleagues conducted a retrospective study of patients treated at the cancer center from 2005 t0 2013. All had metastatic differentiated thyroid cancer and were treated with first-line sorafenib. Some of those who eventually failed treatment with the drug were then given second-line treatment with a different TKI, such as sunitinib (Sutent), pazopanib (Votrient), vemurafenib (Zelboraf), cabozantinib (Cometriq), and lenvatinib.

    Overall, 60 patients were assessed, and the researchers compared those who had sorafenib alone with those who had sorafenib plus salvage therapy.

    They found significantly greater overall survival among patients given salvage therapy with a different TKI than those not given a second-line agent (median 63 months versus 21 months, P=0.013).

    Patients on salvage therapy also had significantly greater progression-free survival, Dadu reported (11.3 months versus 7.4 months)."

    I think this is evidence in favor of AVEO's case that switching TKI's boosted their control arm's survival (even though the indication is totally different).

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    • This raises an interesting issue: if in most cancers switching to just a different TKI after resistance to frontline therapy like Sorafenib fails, such a finding might discount any trial in the salvage space which compares an agent to a pure placebo or a non-TKI control arm.

      • 2 Replies to wildbiftek
      • "...such a finding might discount any trial in the salvage space which compares an agent to a pure placebo or a non-TKI control arm."

        If there is not an approved or "generally accepted" treatment in the indication, placebo is the appropriate control. A positive finding will not be discounted. Other drug sponsors have the opportunity to run trials in the same space.

      • I should say: "if in most cancers we get better survival from switching to just a different TKI after resistance to frontline therapy like Sorafenib fails."

        That said, existing trials like the ones being run for Cabo will at least verify that the treatment works at all. OS and PFS numbers also seem very good in comparison to other TKIs for indications like RCC and HCC, with the caveat of comparing across small, early-stage trials.

 
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