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Accueil Nota Bene Cancer V2 Numéro 135 du 10 May 2012 Dépistage, diagnostic et pronostic BREADCRUMB PUBLICATION

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

Menée sur 67 patients atteints d'un cancer colorectal métastatique, cette étude rétrospective évalue l'association entre la présence de mutations des gènes KRAS, BRAF, PIK3CA et la réponse au cetuximab

  • Journal of Translational Medicine, Vol. 10 (1), pp. 87, 2012 (article en libre accès)

Résumé en anglais :
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 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.

NBC n° 135 du 10 May 2012

Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

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