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Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
Melanoma genetics and treatment
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Melanoma genetics and treatment

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A summary about new treatments for melanoma, based in the diffrent genetic profile of this disease

A summary about new treatments for melanoma, based in the diffrent genetic profile of this disease

Published in: Health & Medicine, Technology
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  • 1. A journey to the world of melanoma genetic and treatmentLorenzo Alonso. Medical Oncology
  • 2. 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).
  • 3. Braf inhibitor resistance
  • 4. Mutations “relevants” BRAF (40-70%) melanomas NRAS: 20% melanomas PTEN: 20-40% melanomas C-Kit: acral(36%), mucosas(39%) and CSD *((28%). GNAQ y GNA11: > 50% uveal melanomas. *CSD: Chronic sun damaged 9
  • 5. C-Kit Mucosal, acral ( 2% each melanomas) and chronic sun damaged areas. Mutación mope important than amplificatión Drugs: Gleevec, Nilotinib, Dasatinib 10
  • 6. 11
  • 7. 12
  • 8. “Killing” the “mad” BRAF loco Vemurafenib Dabrafenib 13
  • 9. BREAK-3 Responses: Dabrafenib 50% DTIC 6% Median Progression-free survival: 5,1 vs 2,7 months for DabrafenibSquamous cell carcinomaVemurafenib 26%Dabrafenib 6% 14
  • 10. N-RAS mutation (MEK 162)GNAQ
  • 11. 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
  • 12. MEK inhibitors.AZD6244: inhibe MEK1 y MEK2 .GSK1120212(trametinib)
  • 13. 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
  • 14. Dabrafenib (antiBRAF) alone or combined with trametinib(MEK inh) Flaherty,K, NEJM 2012;367: 1694
  • 15. The practical path Melanoma diagnosis ECOG 0-1 Ipili o “slow” vemuraipili Braf no Braf mut mut Clinical vemura agressive
  • 16. Braf: Vemurafenib.Dabrafenib MEK: trametinib. MEK 162 cKit: Imanitinib. Dasatinib. NRAS: MEK162 GNAQ: MEK inhCSD: chronic sundamagedUveal: GNAQ 55% GNA11 35%
  • 17. Melanoma genetic variants and therapeuticAnatomicalsite Marker Drugs TrialsSkin: non- Braf (60%) Vemurafenib Phase IIIchronic sun Dabrafenib MEK inh:damaged trametinib NRAS(10%) MEK162 Phase IISkin: sun Kit (25%) Imatinibdamaged Braf (5%) DasatinibMucoses Kit (39%) Phase II NRAS (5%)Acral Kit (36%) Braf (15%) NRAS (10%)Uveal GNAQ MEK inh:trametinib
  • 18. albamumabtrigafenib

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