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.