| General information |
| Database: | DB00022 |
| Objective: | Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the Kras gene in the tumor may affect the response to cetuximab and have treatmentindependent prognostic value |
| Authors: | Karapetis CS, et al |
| Title: | Kras mutations and benefit from cetuximab in advanced colorectal cancer. |
| Journal: | N Engl J Med |
| Year: | 2008 |
| PMID: | 18946061 |
| Trial Design |
| Clinical Trial Id: | NCT00079066 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase III trial |
| Key Patients Feature: | patients with advanced colorectal cancer |
| Biomarker: | KRAS mutation |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | best supportive care alone |
| Treatment Info: | Pts were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone, to look for activating mutations in exon 2 of the Kras gene |
| Primary End Point: | assessed whether the mutation status of the Kras gene was associated with survival in the cetuximab and supportivecare groups. |
| Secondary End Point: | NA |
| Patients Number: | 394 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | progression free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P<0.001). |
| Median OS A vs. C: | In patients with wildtype Kras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001);Among patients with mutated Kras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P=0.89) or progression free survival (hazard ratio, 0.99; P=0.96). In the group of patients receiving best supportive care alone, the mutation status of the Kras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P=0.97). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Patients with a colorectal tumor bearing mutated Kras did not benefit from cetuximab, whereas patients with a tumor bearing wildtype Kras did benefit from cetuximab. The mutation status of the Kras gene had no influence on survival among patients treated with best supportive care alone. |