TY - JOUR
T1 - KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab
AU - Lièvre, Astrid
AU - Bachet, Jean Baptiste
AU - Boige, Valérie
AU - Cayre, Anne
AU - Le Corre, Delphine
AU - Buc, Emmanuel
AU - Ychou, Marc
AU - Bouché, Olivier
AU - Landi, Bruno
AU - Louvet, Christophe
AU - André, Thierry
AU - Bibeau, Fréderic
AU - Diebold, Marie Danièle
AU - Rougier, Philippe
AU - Ducreux, Michel
AU - Tomasic, Gorana
AU - Emile, Jean François
AU - Penault-Llorca, Frédérique
AU - Laurent-Puig, Pierre
PY - 2008/1/20
Y1 - 2008/1/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=38649099966&partnerID=8YFLogxK
U2 - 10.1200/JCO.2007.12.5906
DO - 10.1200/JCO.2007.12.5906
M3 - Article
C2 - 18202412
AN - SCOPUS:38649099966
SN - 0732-183X
VL - 26
SP - 374
EP - 379
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -