Egfr Ca Repeat Polymorphism Predict Clinical Outcome in Egfr Mutation Positive Nsclc Patients Treated with Erlotinib

Abstract

Aim: 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). However, not all patients with EGFR mutations respond to erlotinib and the duration of the response varies markedly between patients. ACA repeat polymorphism in intron 1 of the EGFR gene influences the transcription of the EGFR gene. Here the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib is evaluated. Methods: The number of CA repeats in the EGFR gene was evaluated 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: We demonstrate a significant better 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 EGFR mutation positive patients (N = 62) harboring a short allele versus a long allele (median follow-up time of 52.2 months). The result remained highlysignificant in a multivariate Cox proportional hazards model. This correlation was not seen in EGFR mutation negative patients. Further, there were an association between having a short allele and developing the L585R mutation in exon 21 and between long allele and exon 20 insertions. Conclusions: We 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 longer progression free survival and overall survival. Disclosure: All authors have declared no conflicts of interest.