Outcomes of an Australian testing programme for epidermal growth factor receptor mutations in non-small cell lung cancer.
BACKGROUND
Molecular characterisation of non-squamous non-small-cell lung cancer (NSCLC) is required to direct optimal treatment. Treatment of NSCLC with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (EGFR-TKI) should be guided by the presence of activating mutations of the EGFR gene.


OBJECTIVE
To gain insight into the rate of testing, the range of tissues samples, test utility and outcome when cost of testing as a barrier to access is removed in the Australian setting.


METHODS
In October 2010, a sponsored programme was commenced to gather data on EGFR gene mutation testing in Australia. Partnering laboratories were funded for provision of de-identified results. For participating patients, the programme supported the test charge. Mutation testing was performed using Sanger sequencing of exons 18-21 of the EGFR.


RESULTS
Samples 2013 were submitted from 2012 patients. Full sequencing was achieved in 1717 (85%). Failure of full sequencing was more likely in samples derived from fine needle aspiration(FNA) biopsy than tissue biopsy or pleural/pericardial fluid cell blocks OR 3.1 (95% CI 1.9-5.2). There were 359 mutations seen in 337 patients. 14.5% of cases had a classical mutation conferring sensitivity to EGFR-TKI. In addition there was a range of less common mutations - some predicting responses and others of uncertain significance. 1.4% of cases had mutations associated with non-responsiveness to EGFR-TKI.


CONCLUSIONS
EGFR gene mutation testing is feasible on local and interstate lung cancer samples. The rate of valid test outcomes is high, but FNA samples are associated with more frequent test failure.
Concord Repatriation General Hospital, Sydney, New South Wales, Australia.
M J
MJ
Peters
J J
JJ
Bowden
P
P
Carpenter
J
J
Lewis
B
B
Solomon
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D001706:Biopsy / Q000379:methods; D044963:Biopsy, Fine-Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D009928:Organ Specificity; D018579:Patient Selection; D010490:Pericardial Effusion / Q000166:cytology; D016066:Pleural Effusion, Malignant / Q000166:cytology; D015397:Program Evaluation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
carcinoma; epidermal growth factor; epidermal growth factor/antagonist and inhibitor.; mutation rate; non-small-cell lung; receptor