28 doença metastática - presente & futuro

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28 doença metastática - presente & futuro

  1. 1. Doença Metastática Presente & Futuro
  2. 2. Doença Metastática KPS & Co- morbidades
  3. 3. Doença Metastática KPS & Histologia Co- morbidades
  4. 4. SWOG – Taxano/ Vinca & Histologia N = 741 S9806, S0003, and CDDP/Vin arm of S9308 No difference in any efficacy outcome by histologyHistology N (%) OS PFS Median, Mos Adjusted HR* Median, Mos Adjusted HR* (P Value) (P Value)Adeno 424 (57) 8.5 1.00 (referent) 4.3 1.00 (referent)SCCA 128 (17) 8.4 0.987 (.89)† 4.5 0.986 (.89)‡Large cell 82 (11) 7.9 0.974 (.83) 4.2 1.03 (.81)NSCLC, NOS 107 (14) 9.6 0.971 (.79) 5.0 0.87 (.20)*HR from Cox proportional hazards model with adenocarcinoma as referent, adjusted for sex.†HR for SCCA vs all others combined, OS: 0.995 (95% CI: 0.82-1.21; P = .96).‡HR for SCCA vs all others combined, PFS: 1.01 (95% CI: 0.83-1.22; P = .94)Chansky K, et al. IASLC WCLC 2009. Abstract B2.7
  5. 5. Histology Is Not a Predictor of OS FromAntimicrotubule or Gem-Based Therapy 1.0 All Patients (N = 607) 1.0 VC Patients (N = 201) Proportion Surviving Proportion Surviving Adeno Large cell Adeno Large cell 0.8 Other Squamous 0.8 Other Squamous 0.6 0.6 0.4 0.4 0.2 0.2 0 0 0 6 12 18 24 30 36 0 6 12 18 24 30 36 OS (Mos) OS (Mos) 1.0 PC Patients (N = 201) 1.0 GC Patients (N = 205) Proportion Surviving Proportion Surviving Adeno Large cell Adeno Large cell 0.8 Other Squamous 0.8 Other Squamous 0.6 0.6 0.4 0.4 0.2 0.2 0 0 0 6 12 18 24 30 36 0 6 12 18 24 30 36 OS (Mos) OS (Mos) Scagliotti G, et al. J Thorac Oncol. 2009;4:1568-1571.
  6. 6. JMDB Trial: Cisplatin/Pemetrexed vs Cisplatin/Gemcitabine in Advanced NSCLC Survival Probability 1.0 Median (95% CI) 0.8 CP 10.3 (9.8-11.2) No difference in OS or PFS 0.6 CG 10.3 (9.6-10.9) CP vs CG Adjusted HR (95% CI) 0.4 between study arms 0.2 0.94 (0.84-1.05) 0 0 6 12 18 24 30 Survival Time (Mos) in All Patients Survival Probability 1.0 Median (95% CI) 0.8 CP 11.8 (10.4-13.2) Cis/pem improves OS over cis/gem 0.6 CG 10.4 (9.6-11.2) CP vs CG Adjusted HR (95% CI) 0.4 in non-SCCA (HR: 0.81; P = .005) 0.2 0.81 (0.70-0.94) 0 0 6 12 18 24 30 Survival Time (Mos) in Patients With Nonsquamous Histology Survival Probability 1.0 Median (95% CI) 0.8 CP 9.4 (8.4-10.2) Cis/gem improves OS over cis/pem 0.6 CG 10.8 (9.5-12.1) CP vs CG Adjusted HR (95% CI) in SCCA (HR: 1.23; P = .05) 0.4 0.2 1.23 (1.00-1.51) 0 0 6 12 18 24 30Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551. Survival Time (Mos) in Patients With Squamous Histology
  7. 7. Doença Metastática KPS & Histologia Co- morbidades Biologia Molecular
  8. 8. Tratamento da Doença MetastáticaPrimeiro, determine a Histologia Classifique entre escamoso ou não- escamoso Todos pacientes sem diagnóstico óbvio de escamoso devem ser considerados não- escamosos Céls escamosas P63 positivo & TTF-1 negativo Adenocarcinomas TTF-1 positivo (70%) e P63 negativo
  9. 9. Tratamento da Doença MetastáticaSe escamoso …. – Mutaçao EGFR e testagem para ALK não estão recomendadas• Treatmento – 1 linha: dupla de carboplatin/cisplatina e outro(paclitaxel, docetaxel, gemcitabina, vinorelbina), cetuximab/vinorelbine/cisplatin, • Pemetrexed não recomendado – 2 linnha: docetaxel, erlotinib – 3 linha: erlotinib não recomendado
  10. 10. Tratamento da Doença MetastáticaSe não-escamoso ….• TTF-1 positivo?• NÃO, QT está indicada enquanto aguarda pesquisa de biomarcador• Opções – Carboplatin/pemetrexed – Carboplatin/pemetrexed/bevacizumab (???) – Carboplatin/paclitaxel/bevacizumab – Erlotinib/Geftinib (se positivo para mutação EGFR)
  11. 11. Tratamento da Doença Metastática TTF-1 …. • TTF-1–negative lung adenocarcinomas will be negative for EGFR mutations[1] • Expressed in 71% to 76% of adenocarcinomas[2] • No or very low staining in squamous and large-cell carcinomas[3]1. Somaiah N, et al. World Conference on Lung Cancer 2011. Abstract O38.02.2. Di Loreto C, et al. J Clin Pathol. 1997;50:30-32.3. Fabbro D, et al. Eur J Cancer. 1996;32A:512-517.
  12. 12. Tratamento da Doença Metastática EGFR Mutation and TTF-1 Status: Negative Predictive Value • NPV is dependent on the prevalence of EGFR mutations • NPV for a TTF-1 negativity to predict for EGFR mutation–negative status – For an estimated 13% prevalence • 99.5% (95% CI: 98.6% to 99.9%) – For an estimated 15% prevalence • 99.4% (95% CI: 98.4% to 99.9%)Somaiah N, et al. ASCO 2011. Abstract 7530.

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