Epidermal growth factor receptor polymorphisms and clinical outcomes in non-small-cell lung cancer patients treated with gefitinib.
The-216G/T, -191C/A, intron 1 and Arg497Lys epidermal growth factor receptor (EGFR) polymorphisms were evaluated in 92 advanced non-small-cell lung cancer patients treated with gefitinib, an EGFR tyrosine-kinase inhibitor. Improved progression free survival (PFS) was found in patients homozygous for the shorter lengths of intron 1 polymorphism (S/S; S=16 or fewer CA repeats; log-rank test (LRT) P=0.03) and for patients carrying any T allele of the -216G/T polymorphism (LRT, P=0.005). When considered together, patients with intron 1 S/S genotype and at least one T allele of -216G/T had improved PFS (LRT P=0.0006; adjusted hazard ratio (AHR), 0.60 (95% confidence interval, 0.36-0.98)) and overall survival (LRT P=0.02; AHR, 0.60 (0.36-1.00)) when compared with all others. The T allele of -216G/T was also associated with significantly higher rates of stable disease/partial response (P=0.01) and a significantly higher risk of treatment-related rash/diarrhea (P=0.004, multivariate model). EGFR intron 1 and -216G/T polymorphisms influence clinical outcomes in gefitinib-treated non-small-cell lung cancer patients.
Liu
G
G
Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center and Hematology-Oncology Division, Massachusetts General Hospital, Boston, MA, USA. Geoffrey.Liu@uhn.on.ca
Gurubhagavatula
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S
Zhou
W
W
Wang
Z
Z
Yeap
B Y
BY
Asomaning
K
K
Su
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L
Heist
R
R
Lynch
T J
TJ
Christiani
D C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D003967:Diarrhea / Q000139:chemically induced / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005076:Exanthema / Q000139:chemically induced / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006720:Homozygote; D006801:Humans; D007438:Introns; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib