1 Department of Clinical Medicine - The Department of Oncology, Department of Clinical Medicine, Health, Aarhus University2 Department of Clinical Medicine - Clinical Biochemistry, Department of Clinical Medicine, Health, Aarhus University3 Department of Clinical Medicine - Klinisk Biokemisk Afdeling, THG, Department of Clinical Medicine, Health, Aarhus University4 Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, Aarhus University, Aarhus University5 Department of Clinical Medicine - Clinical Biochemistry, Department of Clinical Medicine, Health, Aarhus University6 Department of Clinical Medicine - The Department of Oncology, Department of Clinical Medicine, Health, Aarhus University
OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib.MATERIALS AND METHODS: Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based on the somatic EGFR mutation status.RESULTS: In EGFR mutation positive patients (N=62) we demonstrate a significantly higher median progression free survival (HR=0.39 (0.22-0.70); p=0.002) and overall survival (HR=0.43 (0.23-0.78); p=0.006) in patients also harboring a short CA repeat length vs. a long (median follow-up time of 52.2 months). The result remained highly significant in a multivariate Cox proportional hazards model. This correlation was not seen in EGFR mutation negative patients.CONCLUSION: Our study demonstrate that in EGFR mutation positive NSCLC patients treated with erlotinib a low number of CA repeats in intron 1 of the EGFR gene is a predictor for both longer progression free survival and overall survival.