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What anti-tumor response rate should be anticipated from BRAF inhibition?

What anti-tumor response rate should be anticipated from BRAF inhibition?. A nd how should response best be assessed?. Vemurafenib or DTIC (BRIM3 ): Best t umor r esponse by individual p atient. Sum of t umor d iameters (% change from b aseline ). >100. M1c.

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What anti-tumor response rate should be anticipated from BRAF inhibition?

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  1. What anti-tumor response rate should be anticipated from BRAF inhibition? And how should response best be assessed?

  2. Vemurafenib or DTIC (BRIM3):Best tumor response by individual patient Sum of tumor diameters (% change from baseline ) >100 M1c Vemurafenib: 48.4% response 50 0 -50 -100 >100 DTIC: 5.5% response 50 0 -50 -100 Chapman et al, N Engl J Med 2011; 364: 2507-2516

  3. BRAFi-naïve patients:Investigator-assessed maximum tumor reduction withcombined BRAF / MEK inhibition Maximum reduction frombaseline measurement (%) 100 Dabrafenib 150 mg BID/Trametinib 2mg QD Best unconfirmed response 80 Complete response 60 Partial response Stable disease 40 Progressive disease 20 Part B Part C 0 –20 –40 –60 –80 –100 Sosman et al, ASCO 2013; 9005

  4. Response rates with BRAF inhibition The BRAF inhibitors all have ~50% response rate, with few CRs 80–90% of patients will have stable or regressed disease Results seen similar with vemurafenib, dabrafenib, and LGX 818 RECIST is the most reasonable system devised to assess response with BRAF inhibition

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