EGFR mutations and HER2/3 protein expression and clinical outcome in Chinese advanced non-small cell lung cancer patients treated with gefitinib.
BACKGROUND
To assess the role of various epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression as predictive markers of responsiveness to gefitinib therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).


METHODS
A total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen received gefitinib 250 mg once daily. All the 106 tumors from these patients were screened for mutations in the EGFR exons 18-24, and 84 tumors were studied by immunohistochemistry for HER2/3 expression and correlated with clinical treatment outcome.


RESULTS
Patients with EGFR mutations had a significantly higher overall response rate (ORR), longer time to progression (TTP) and overall survival (OS) compared with those with wild-type receptor. No difference in ORR was observed between patients with exon 19 deletion and patients with other EGFR mutations. ORR in HER2-positive patients was significantly higher than in the HER2-negative group, irrespective of EGFR mutational status, and a trend for better ORR was observed for HER3-positive patients. HER2 and HER3 expression levels were not associated with any difference in terms of TTP and OS. Nevertheless, when considering the subgroups of non-responders to gefitinib, median TTP in patients with mutated EGFR was significantly longer than in those with no mutations (8.0 vs. 3.0 months, P = 0.0065). EGFR-mutated patients had no significant difference in ORR, TTP and OS according to HER2 and/or HER3 expression.


CONCLUSIONS
EGFR mutations are effective predictors for gefitinib efficacy in Chinese patients with advanced NSCLC. HER2 and HER3 expression does not provide any additional information for selecting patients most likely to benefit from gefitinib treatment.
Xu
Jian Ming
JM
Beijing 307 Hospital Cancer Center, No. 8 Dong Da Street, Feng Tai District, 100071, Beijing, China, jmxu2003@yahoo.com.
Han
Yu
Y
Duan
Hai Qing
HQ
Gao
E Mei
EM
Zhang
Yang
Y
Liu
Xiao Qing
XQ
Zhang
Jing Sheng
JS
Toschi
Luca
L
Galetta
Domenico
D
Azzariti
Amalia
A
Paradiso
Angelo
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002681:China; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077156:Gefitinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3