Antitumoral activity of tyrosine kinase inhibitors in patients with non-small cell lung cancer harbouring rare epidermal growth factor receptor mutations.
BACKGROUND
Mutations in the epidermal growth factor receptor (EGFR) have been reported as predictive markers of tumour response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Although the "common" EGFR mutations have been associated with response to EGFR-TKIs, the correlation with response to treatment for many other rare mutations is still unclear. The aim of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR-TKIs in this selected group of patients.


METHODS
Three hundred and thirty patients with stage IIIB/IV NSCLC (106 females aged 62.5 ± 1.1 years; 224 males aged 68.0 ± 0.6 years) were enrolled in the study. Formalin fixed paraffin embedded tissue samples were screened for mutations using a high resolution melting technique, followed by Sanger sequencing of exons 18-21 of the EGFR-gene. Mutation status was also tested using the Roche Cobas(®) EGFR mutation test.


RESULTS
EGFR mutations were detected in 31 tumours (9.4 %). Eleven cases carried novel mutations, six of these patients were treated with erlotinib or gefitinib. A response rate (RR) of 50.0 % was obtained in the group with rare EGFR mutations, the PFS was 3.0 months [standard deviation (STD) = 5.4 months]. The RR to EGFR-TKIs in patients with conventional EGFR mutations was 85 % with a median PFS of 10.5 months (STD = 3.6 months).


CONCLUSIONS
We reported six patients with rare EGFR mutations of unknown clinical significance and their association with EGFR-TKIs. Report of cases harbouring rare mutations can support the decision making progress in this subset of patients.
Department of Molecular Diagnostics, AZ Delta Roeselare Menen, Ardooisesteenweg 276, 8800, Roeselare, Belgium. matthijsoyaert@telenet.be.
Matthijs
M
Oyaert
Department of Pneumology, Center for Thoracic Oncology, AZ Delta Roeselare Menen, Roeselare, Belgium.
Ingel
I
Demedts
Department of Molecular Diagnostics, AZ Delta Roeselare Menen, Ardooisesteenweg 276, 8800, Roeselare, Belgium.
Elke
E
Boone
Department of Pathology, AZ Delta Roeselare Menen, Roeselare, Belgium.
Franceska
F
Dedeurwaerdere
Department of Pathology, AZ Delta Roeselare Menen, Roeselare, Belgium.
Jo
J
Vandorpe
Department of Molecular Diagnostics, AZ Delta Roeselare Menen, Ardooisesteenweg 276, 8800, Roeselare, Belgium.
Emmanuel
E
De Laere
Department of Molecular Diagnostics, AZ Delta Roeselare Menen, Ardooisesteenweg 276, 8800, Roeselare, Belgium.
Joke
J
Breyne
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib