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

3. The hard fact 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 Data collected using PubMed; search criteria ‘melanoma clinical trial’

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

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

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

7. ipi and vem in phase 2 testing as second line therapy for metastatic melanoma Ipi phase 2Vem phase 2 No. patients155132 Response rate5.8%53% Median OS10.2 months15.9 months Toxic deaths5 patients0 patients Journal publication O’Day et al. 2010 Annals Oncology (IF 6.45) Sosman et al. 2012 NEJM (IF 53.48) 10 times higher 6 months longer

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

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

10. Time to response and progression according to baseline LDH Less aggressive melanomas, more frequent durable responses More aggressive melanomas, unlikely to respond to ipi but had benefit with vem

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

12. Conclusions Only 3 agents have improved OS in metastatic melanoma after >3000 clinical trials In patients with BRAF V600 mutant metastatic melanoma, BRAF inhibitors should be the first line choice of therapy