KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients

Maurizio Martini, Alessandra Cassano, Luigi Maria Larocca, Michele Basso, Antonia Strippoli, Armando Orlandi, Maria Alessandra Calegari, Giovanni Schinzari, Mariantonietta Di Salvatore, Tonia Cenci, Carlo Antonio Barone

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Background: In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1). Methods: Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6±bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression. Results: Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P¼0.008) and when only patients receiving FOLFOX-6±bevacizumab as first-line are considered (P¼0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P¼0.001) and in those treated as first-line (10 vs 8 months, respectively, P¼0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P¼0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis. Conclusion: Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.
Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalBritish Journal of Cancer
Volume108
DOIs
Publication statusPublished - 2013

Keywords

  • Colorectal cancer
  • ERCC1
  • KRAS
  • Oxaliplatin

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