B113
KRAS genotyping and second line therapy for non small cell lung cancer
Amna Sheri, Kate Young, Robert Goldstein, Sue Ashley, James Myerson, Martina Puglishi, Leonardo Trani, Mary O'Brien, Sanjay Popat
Royal Marsden Hospital, London, UK
Background
Erlotinib is licensed for use as a second line treatment for patients with Non Small Cell Lung Cancer (NSCLC) and is approved by NICE as an alternative to docetaxel. Response to Erlotinib is heterogeneous and has been shown to correlate with a number of clinical factors. Molecular profiles have also been investigated as potential predictive indicators of patient response. Somatic mutations of the K-ras oncogene at codons 12 and 13 have been assessed as a mechanism of denovo resistance to EGFR Tyrosine Kinase inhibition in patients with NSCLC. Several studies have demonstrated a significant inverse association between response to Erlotinib and somatic K-ras mutation.
Aim
To conduct a prospective audit in patients with NSCLC at the Royal Marsden Hospital to evaluate the proportion of patients receiving Erlotinib as second line therapy and to analyze the variables influencing the clinical decision making process. To establish how many patients can be genotyped for K-ras and the proportion that have mutations. To then describe the response to treatment according to K-ras status.
Method
Data from 50 consecutive patients receiving second line treatment for NSCLC was collected and analysed from the prospectively maintained lung unit research database and electronic patient records. All available tissue was reviewed and gentoyped for K-ras mutational status.
Results
Data on the choice of second line therapy, outcome and the feasibility of incorporating K-ras genotyping into the decision making process will be presented.
Data from 50 patients has been collected with genotyping being performed where tissue is sufficient. To date, genotyping has been possible for 44% of patients whose histology has been reviewed. Further data to be presented at the meeting.
Conclusion
Further analysis will reveal whether the K-ras genotype can help us predict response over and above the clinical factors previously used in treatment decisions. By identifying patients who may do worse than expected on Erlotinib, our patient selection process would be improved. However, obtaining sufficient tissue for genotyping may be problematic and if the mutation detection rate is low, use in the clinic may be limited.
