Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?
OBJECTIVE
This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib.


METHODS
One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry.


RESULTS
The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (gamma = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89).


CONCLUSIONS
Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.
Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine.
Myung-Ju
MJ
Ahn
Byeong-Bae
BB
Park
Jin Seok
JS
Ahn
Sang We
SW
Kim
Heung-Tae
HT
Kim
Jong Seog
JS
Lee
Jin Hyung
JH
Kang
Jae Yong
JY
Cho
Hong Suk
HS
Song
Se Hoon
SH
Park
Chang Hak
CH
Sohn
Sang Won
SW
Shin
Jin Hyuck
JH
Choi
Chang-Seok
CS
Ki
Chan Keum
CK
Park
Alison J
AJ
Holmes
Pasi A
PA
Jänne
Keunchil
K
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride