1319P - EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Translational Research
Presenter Anne Larsen
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors A.W. Larsen1, P.H. Nissen1, P. Meldgaard2, B.S. Sorensen1
  • 1Department Of Clinical Biochemistry, Aarhus University Hospital, 8000 - Aarhus C/DK
  • 2Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus/DK

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. A CA 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 highly significant 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.