Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer.
BACKGROUND
The presence of EGFR (epidermal growth factor receptor) mutations is a robust predictor of EGFR tyrosine kinase inhibitor (TKI) responsiveness. Predictors of EGFR-TKI responsiveness in EGFR-mutant non-small cell lung cancer (NSCLC) patients, however, have not been well investigated. The purpose of this study is to examine predictors of EGFR-TKI responsiveness in EGFR-mutant NSCLC patients.


METHODS
Seventy EGFR-mutant NSCLC patients who received EGFR-TKIs in our institution between April 2007 and March 2013 were analyzed retrospectively.


RESULTS
The objective response rate was 50.0% (95% confidence interval, CI, 38.6-61.4%) and the disease control rate was 91.4% (95% CI, 82.5-96.0%). The median progression-free survival (PFS) and overall survival were 9.0 (95% CI, 3.92-14.08) and 20.8 months (95% CI, 14.56-27.04), respectively. In multivariate analysis, adenocarcinoma (hazard ratio, HR, 12.25; 95% CI, 37.7-41.10; p < 0.001) and major mutations (deletions in exon 19 and L858R point mutation in exon 21; HR, 2.46; 95% CI, 1.14-5.28; p = 0.022) were significant predictors of longer PFS.


CONCLUSIONS
Major mutations and adenocarcinoma histology were independent predictors of better treatment outcome in EGFR-mutant NSCLC patients who received EGFR-TKIs. Further well-controlled prospective studies are warranted to confirm our findings.
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.
Jun
J
Fukihara
Naohiro
N
Watanabe
Hiroyuki
H
Taniguchi
Yasuhiro
Y
Kondoh
Tomoki
T
Kimura
Kensuke
K
Kataoka
Toshiaki
T
Matsuda
Toshiki
T
Yokoyama
Yoshinori
Y
Hasegawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib