Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

Giuseppe Bronte, Antonio Russo, Francesco Pantano, Fotios Loupakis, Alice Zoccoli, Marco Imperatori, Emanuela Dell'Aquila, Andrea Onetti-Muda, Elena Ongaro, Andrea Onetti-Muda, Daniele Rossini, Giuseppe Perrone, Francesco Mannavola, Erica Bonazzina, Chiara Cremolini, Giovanna De Maglio, Giuseppe Aprile, Bruno Vincenzi, Giovanna De Maglio, Gabriella FontaniniAlfredo Falcone, Salvatore Siena, Clara Natoli, Giuseppe Tonini, Daniele Santini, Andrea Sartore-Bianchi, Daniele Santini, Giuseppe Perrone

Risultato della ricerca: Articlepeer review

23 Citazioni (Scopus)

Abstract

Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/ tumor sample, are available. We aimed to evaluate the prognostic value of K-Ras mutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.
Lingua originaleEnglish
pagine (da-a)31604-31612
Numero di pagine9
RivistaOncotarget
Volume6
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology

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