A journey to the world of melanoma genetic and treatmentLorenzo Alonso. Medical Oncology
The Facts• Phase III vemurafenib vs DTIC: median OS 13,2 months vs 9,6 months(significant)• 12 months OS: vemurafenib 55% vs 43% for dacarbazine.• Duration of response limited due to development of resistance• Ipilimumab: objective response uncommon(10-20%). Median OS vs gp100 10 vs 6,4 months. In a second study vs DTIC 3 year estimated survival rates 21% vs 12% (HR 0,72).
Lancet Oncology 2013; 14: 249 End-point response: 30patients 20%PR in NRAS mutated Previous treatment allowed: no MEK inh or Ipilimumab The most common grade 3-4 adverse event: an asymptomatic rise in CPK “Retinal events” also commons
MEK inhibitors.AZD6244: inhibe MEK1 y MEK2 .GSK1120212(trametinib)
METRIC: Trametinib vs chemotherapy (Braf mutated) Chemotherapy:DTIC or Taxol 47% chemotherapy arm crossed over to trametinib At least one previous regimen No Braf inh or Ipilimumab allowedResponse rate: 22% vs 8% Flaherty,K. NEJM 2012; 367:107
Dabrafenib (antiBRAF) alone or combined with trametinib(MEK inh) Flaherty,K, NEJM 2012;367: 1694
The practical path Melanoma diagnosis ECOG 0-1 Ipili o “slow” vemuraipili Braf no Braf mut mut Clinical vemura agressive