Cetuximab ( Erbitux ) is efficient in advanced colorectal cancer ( CRC ). Researchers previously showed that KRAS mutations were associated with resistance to Cetuximab in 30 CRC patients.
The aim of a study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to Cetuximab and survival.
Eighty-nine metastatic patients with advanced colorectal cancer 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.
A KRAS mutation was present in 27% of the patients and was associated with resistance to Cetuximab ( 0% vs 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P less than 0.001 ) and a poorer survival ( median PFS: 10.1 vs 31.4 weeks in patients without mutation; P=0.0001; median OS: 10.1 vs 14.3 months in patients without mutation; P=0.026 ).
When researchers pooled these 89 patients with patients from previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with overall survival and progression-free survival, whereas skin toxicity was only associated with overall survival.
In a combined analysis, median overall survival 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.
In conclusion, these results confirm the high prognostic value of KRAS mutations on response to Cetuximab and survival in metastatic patients with advanced colorectal cancer, treated with Cetuximab. ( Xagena )
Lièvre A et al, J Clin Oncol 2008; 26: 374-379