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What should patients with BRAF mutant melanoma receive as front line therapy?

What should patients with BRAF mutant melanoma receive as front line therapy?. Antoni Ribas, M.D. Professor of Medicine Professor of Surgery Professor of Molecular and Medical Pharmacology Director, Tumor Immunology Program, Jonsson Comprehensive Cancer Center (JCCC)

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What should patients with BRAF mutant melanoma receive as front line therapy?

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  1. What should patients with BRAF mutant melanoma receive as front line therapy? Antoni Ribas, M.D. Professor of Medicine Professor of Surgery Professor of Molecular and Medical Pharmacology Director, Tumor Immunology Program, Jonsson Comprehensive Cancer Center (JCCC) University of California Los Angeles (UCLA) Chair, Melanoma Committee at SWOG

  2. Let’s stick to the facts of melanoma treatment Discuss melanoma treatments with Mike Atkins…

  3. After >40 years of modern medical oncology and >3,000 clinical trials, only 3 agents have improved overall survival (OS) in melanoma: ipilimumab vemurafenib trametinib The hard fact Data collected using PubMed; search criteria ‘melanoma clinical trial’

  4. BRAF MEK ERK Cancer growth and survival Vemurafenib, an on target therapy to block the driver cancer signal

  5. BRAF MEK ERK Cancer growth and survival Vemurafenib, an on target therapy to block the driver cancer signal

  6. BRAF MEK ERK ipilimumab Cancer growth and survival Vemurafenib, an on target therapy to block the driver cancer signal

  7. ipi and vem in phase 2 testing as second line therapy for metastatic melanoma 10 times higher 6 months longer 10 times higher

  8. OS HR = 0.66 HR = 0.72 HR = 0.37 Time to results > 3 years > 3 years 1 month

  9. PFS HR = 0.64 HR = 0.76 HR = 0.26

  10. Time to response and progression according to baseline LDH Less aggressive melanomas, more frequent durable responses Time on study by LDH level at baseline Normal More aggressive melanomas, unlikely to respond to ipi but had benefit with vem 1.0-1.5 x ULN Time on study >1.5 x ULN Time to response Time to response Progressive disease Progressive disease Continued response Continued response 0 2 4 6 8 10 12 14 16 Time (months) Approx timing of CT assessments Median duration of response = 6.7 months (95% CI: 5.6, 9.8; range 1.3–12.7)

  11. Let me think about this? Eureka!! Je le trouve To vem or not to vem? this is the question

  12. Conclusions • Only 3 agents have improved OS in metastatic melanoma after >3000 clinical trials • In patients with BRAFV600 mutant metastatic melanoma, BRAF inhibitors should be the first line choice of therapy

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