Keunchil Park

1
Introduction

• Keunchil Park
• Samsung Medical Center,Seoul, Korea

2
EGFR an important target for NSCLC treatment
Extracellular
Intracellular
P
P
JNK
PI3K Akt
MAPK

• Proliferation
• Invasion
• Metastasis
• Angiogenesis
• Inhibition of apoptosis

Woodburn JR. Pharmacol Ther 19998224150 Lynch
TJ, et al. N Engl J Med 2004350212939Knowlden
JM, et al. Endocrinology 2003144103244Chakrav
arti A, et al. Cancer Res 200262430715
3
Tarceva a potent oral inhibitor of EGFR
Moyer JD, et al. Cancer Res 199757483848Stamos
J, et al. J Biol Chem 20022774626572
4
NCIC-CTG BR.21 study design
Tarceva150mg daily
R A N D M I S E

• Stage IIIB/IV NSCLC
• Failed prior chemotherapy
• not eligiblefor further chemotherapy
• PS 03

Placebo
NCIC-CTG National Cancer Institute of
Canada-Clinical Trials GroupPS performance
status
5
BR.21 overall survival
1.00 0.75 0.50 0.25 0
HR0.73, plt0.001
Survival distribution function

• 42.5 improvement in median survival

Tarceva Placebo
0 5 10 15 20 25 30
Months
HR and p (log-rank test) adjusted for
stratification factors at randomisation and EGFR
status
Shepherd FA, et al. N Engl J Med 200535312332
6
Tarceva post BR.21

• Approved in over 80 countries worldwide
• As with all other therapies, some patients
  benefit more from Tarceva than others
• how do we identify these patients?
• Selection of specific patients appears to play a
  large role in the clinical use of Tarceva
• Is patient selection supported by robust clinical
  evidence?
• review the myths and facts surrounding the use of
  Tarceva in second-line treatment of advanced NSCLC