Access : ERCC1|[sol]|BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin : British Journal of Cancer

Access : ERCC1|[sol]|BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin : British Journal of Cancer

British Journal of Cancer , (2 April 2013) | doi:10.1038/bjc.2013.127

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  • M Tiseo
  
  
  • P Bordi
  
  
  • B Bortesi
  
  
  • L Boni
  
  
  • C Boni
  
  
  • E Baldini
  
  
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ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin

M Tiseo, P Bordi, B Bortesi, L Boni, C Boni, E Baldini, F Grossi, F Recchia, F Zanelli, G Fontanini, N Naldi, N Campanini, C Azzoni, C Bordi, A Ardizzoni and on behalf of Bio-FAST trial group

Abstract

Background:

The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1–3 gene polymorphisms on outcomes of patients was examined.

Methods:

Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.

Results:

Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).

Conclusion:

This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.