Doença Metastática
Presente & Futuro
Doença Metastática
KPS &Co-
morbidades
Doença Metastática
KPS &Co-
morbidades
Histologia
SWOG – Taxano/ Vinca & Histologia
Histology N (%) OS PFS
Median, Mos Adjusted HR* (P Value)
Median, Mos Adjusted HR* (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
N = 741
S9806, S0003, and CDDP/Vin arm of S9308
No difference in any efficacy outcome by histology
OS (Mos)
Pro
po
rtio
n S
urv
ivin
g
0
0.4
0.6
0.8
1.0
0.2
All Patients (N = 607)
AdenoOther
Large cellSquamous
0 6 12 18 24 30 36
OS (Mos)
Pro
po
rtio
n S
urv
ivin
g
0
0.4
0.6
0.8
1.0
0.2
PC Patients (N = 201)
AdenoOther
Large cellSquamous
0 6 12 18 24 30 36
OS (Mos)
Pro
po
rtio
n S
urv
ivin
g
0
0.4
0.6
0.8
1.0
0.2
VC Patients (N = 201)
AdenoOther
Large cellSquamous
0 6 12 18 24 30 36
OS (Mos)
Pro
po
rtio
n S
urv
ivin
g
0
0.4
0.6
0.8
1.0
0.2
GC Patients (N = 205)
AdenoOther
Large cellSquamous
0 6 12 18 24 30 36
Histology Is Not a Predictor of OS From Antimicrotubule or Gem-Based Therapy
Scagliotti G, et al. J Thorac Oncol. 2009;4:1568-1571.
No difference in OS or PFS between study arms
Cis/pem improves OS over cis/gemin non-SCCA (HR: 0.81; P = .005)
Cis/gem improves OS over cis/pemin SCCA (HR: 1.23; P = .05)
Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551.
Survival Time (Mos) in All Patients
Su
rviv
al P
rob
abili
ty
0
0.2
0.6
1.0
0.4
0.8 CPCG
0 6 12 18 24 30
Median (95% CI)10.3 (9.8-11.2)10.3 (9.6-10.9)
Adjusted HR (95% CI)0.94 (0.84-1.05)
CP vs CG
Survival Time (Mos) in Patients With Nonsquamous Histology
Su
rviv
al P
rob
abili
ty
0
0.2
0.6
1.0
0.4
0.8 CPCG
0 6 12 18 24 30
Median (95% CI) 11.8 (10.4-13.2)10.4 (9.6-11.2)
Adjusted HR (95% CI) 0.81 (0.70-0.94)
CP vs CG
Survival Time (Mos) in Patients With Squamous Histology
Su
rviv
al P
rob
abili
ty0
0.2
0.6
1.0
0.4
0.8 CPCG
0 6 12 18 24 30
Median (95% CI) 9.4 (8.4-10.2)10.8 (9.5-12.1)
Adjusted HR (95% CI) 1.23 (1.00-1.51)
CP vs CG
JMDB Trial: Cisplatin/Pemetrexed vs Cisplatin/Gemcitabine in Advanced NSCLC
Doença Metastática
KPS &Co-
morbidades
BiologiaMolecular
Histologia
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
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
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)
Tratamento da Doença MetastáticaTTF-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.
Tratamento da Doença MetastáticaEGFR 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.