PURPOSE: Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. PATIENTS AND METHODS: Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed. RESULTS: A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively. CONCLUSION: These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.
PURPOSE:Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRCpatients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. PATIENTS AND METHODS: Eighty-nine metastatic CRCpatients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed. RESULTS: A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively. CONCLUSION: These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRCpatients treated with cetuximab.
Authors: Efsevia Vakiani; Manickam Janakiraman; Ronglai Shen; Rileen Sinha; Zhaoshi Zeng; Jinru Shia; Andrea Cercek; Nancy Kemeny; Michael D'Angelica; Agnes Viale; Adriana Heguy; Philip Paty; Timothy A Chan; Leonard B Saltz; Martin Weiser; David B Solit Journal: J Clin Oncol Date: 2012-06-04 Impact factor: 44.544
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Authors: David Liska; Chin-Tung Chen; Thomas Bachleitner-Hofmann; James G Christensen; Martin R Weiser Journal: Clin Cancer Res Date: 2010-11-22 Impact factor: 12.531
Authors: Todd M Pitts; Aik Choon Tan; Gillian N Kulikowski; John J Tentler; Amy M Brown; Sara A Flanigan; Stephen Leong; Christopher D Coldren; Fred R Hirsch; Marileila Varella-Garcia; Christopher Korch; S Gail Eckhardt Journal: Clin Cancer Res Date: 2010-06-08 Impact factor: 12.531
Authors: Bruno Vincenzi; Chiara Cremolini; Andrea Sartore-Bianchi; Antonio Russo; Francesco Mannavola; Giuseppe Perrone; Francesco Pantano; Fotios Loupakis; Daniele Rossini; Elena Ongaro; Erica Bonazzina; Emanuela Dell'Aquila; Marco Imperatori; Alice Zoccoli; Giuseppe Bronte; Giovanna De Maglio; Gabriella Fontanini; Clara Natoli; Alfredo Falcone; Daniele Santini; Andrea Onetti-Muda; Salvatore Siena; Giuseppe Tonini; Giuseppe Aprile Journal: Oncotarget Date: 2015-10-13