Predictive role of multiple gene alterations in response to cetuximab in metastatic colorectal cancer: A single center study

Paola Ulivi, Laura Capelli, Martina Valgiusti, Wainer Zoli, Emanuela Scarpi, Elisa Chiadini, Paola Rosetti, Sara Bravaccini, Daniele Calistri, Luca Saragoni, Andrea C. Gardini, Angela Ragazzini, Giovanni L. Frassineti, Dino Amadori, Alessandro Passardi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen.Methods: 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry.Results: BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respectively) and OS (p = 0.008 and p = 0.029, respectively). No differences in clinical outcome were found between patients who were positive or negative for PTEN expression. Conversely, patients negative for KRAS, BRAF and PIK3CA mutations were characterized by significantly better ORR, PFS and OS than patients with at least one of these mutations.Conclusions: BRAF and PIK3CA mutations would seem to be independent predictors of anti-EGFR therapy effectiveness and could be taken into consideration during treatment decision making.

Original languageEnglish
Article number87
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - May 8 2012

Keywords

  • BRAF
  • Cetuximab
  • KRAS
  • Metastatic colorectal cancer
  • PIK3CA
  • PTEN

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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