Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT

M. Di Bartolomeo, F. Pietrantonio, F. Perrone, K. F. Dotti, A. Lampis, C. Bertan, E. Beretta, L. Rimassa, C. Carbone, P. Biondani, R. Passalacqua, S. Pilotti, E. Bajetta

Research output: Contribution to journalArticle

Abstract

There is conflicting evidence on the predictive role of KRAS status when cetuximab is added to oxaliplatin-based regimens. This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients enrolled in TEGAFOX-E (cetuximab, oxaliplatin and oral uracil/ftorafur-UFT) phase II study. Twenty-eight patients were enrolled and all were evaluable for safety and activity. Twenty-three specimens were analysed for KRAS, BRAF, NRAS, PI3KCA and TP53 mutational status by means of polymerase chain reaction and correlated with objective response, progression-free survival and overall survival. An evident increase of response rate was noted in KRAS/NRAS wild-type cases (70 versus 33 %, P=0.198). KRAS/NRAS wild-type status showed an independent association with a longer progression-free survival (44 versus 9 weeks, P=0.009). Considering the combined assessment of BRAF, KRAS/NRAS and TP53, a trend towards an increase of response rate was noted in patients without mutations (83 versus 33 %, P=0.063). Moreover, patients with all wild-type genes had significantly longer progression-free survival than patients with any mutation (48 versus 10 weeks, P=0.007). As a single biomarker, only KRAS/NRAS proteins maintained an independent value for outcome prediction. Patients with KRAS/NRAS, BRAF and TP53 wild-type tumours could derive the maximal benefits from treatment with cetuximab, oxaliplatin and UFT.

Original languageEnglish
Pages (from-to)155-162
Number of pages8
JournalTargeted Oncology
Volume9
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Biomarkers
  • BRAF
  • Cetuximab
  • Chemotherapy
  • Colorectal cancer
  • KRAS
  • TP53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Pharmacology (medical)
  • Medicine(all)

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