Dominance of EGFR and insignificant KRAS mutations in prediction of tyrosine-kinase therapy for NSCLC patients stratified by tumor subtype and smoking status.
BACKGROUND
Therapy by tyrosine kinase inhibitors (TKI) has become inevitable in treatment of advanced NSCLC. Mutations in EGFR and KRAS genes have been identified as the main potential predictive and prognostic factors. Here the clinical implications of EGFR/KRAS mutations in patients from two separate trials treated with gefitinib or erlotinib are analysed.


METHODS
A total of 360 patients (269 gefitinib and 91 erlotinib) were evaluated. Mutations in EGFR (exon 19 and 21) and KRAS (codons 12 and 13) and their impact on response and survival with respect to tumor subtype and smoking status were assessed.


RESULTS
Adenocarcinomas revealed 399 days to progression (TTP) and 548 days overall survival (OS) for EGFR mutated vs. 119 days to progression and 137 days survival for non-mutated, p<0.0001 (TTP) and p=0.0001 (OS). No EGFR effect was recorded for squamous cell tumors. For smoking status, both EGFR-mutated smokers and non-smokers profited from TKI therapy. Smokers: 243 vs. 122 days (mutated vs. non-mutated), p=0.0284 (TTP) and 244 vs. 126 days, p=0.0396 (OS); non-smokers: 390 vs. 71 days, p<0.0001, (TTP) and 548 vs. 135 days, p<0.0001 (OS). KRAS mutation in tumors did not result in a poorer prognosis in the subtype-selected groups, nor did it present as a negative factor in smokers.


CONCLUSIONS
EGFR mutations possess statistical significance for a better therapy response and longer survival in all patients with adenocarcinomas (smokers as well as non-smokers). KRAS does not seem an "a priori" negative factor for TKI-based treatment of NSCLC.
Pesek
Milos
M
Departments of Pneumology, Faculty Hospital Pilsen, Pilsen, Czech Republic.
Benesova
Lucie
L
Belsanova
Barbora
B
Mukensnabl
Petr
P
Bruha
Frantisek
F
Minarik
Marek
M
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003062:Codon; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012907:Smoking; D016019:Survival Analysis
D003062:Codon; D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases