| General information |
| Database: | DB00023 |
| Objective: | The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as firstline treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wildtype disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken. |
| Authors: | Van Cutsem E, et al |
| Title: | Cetuximab plus irinotecan, fluorouracil, and leucovorin as firstline treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. |
| Journal: | J Clin Oncol |
| Year: | 2011 |
| PMID: | 21502544 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Cetuximab + irinotecan, fluorouracil+leucovorin |
| Study Type: | an openlabel, randomized, multicenter, phase III study |
| Key Patients Feature: | pts with metastatic colorectal cancer (mCRC) |
| Biomarker: | KRAS mutation |
| Biomark Analysis: | The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a potheyrful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis. |
| Control Group Info: | FOLFIRI alone |
| Treatment Info: | patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slidemounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series. |
| Primary End Point: | PFS. |
| Secondary End Point: | overall survival, best overall response, and safety. A retrospective subgroup analysis investigated associations between tumor KRAS mutation status and outcome. |
| Patients Number: | 1198 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The addition of cetuximab to FOLFIRI in patients with KRAS wildtype disease resulted in significant improvements in response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The addition of cetuximab to FOLFIRI in patients with KRAS wildtype disease resulted in significant improvements in progression free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), |
| Median OS A vs. C: | The addition of cetuximab to FOLFIRI in patients with KRAS wildtype disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio [HR], 0.796; P = .0093), |
| Adverse Event(agent arm): | NA |
| Conclusions: | The addition of cetuximab to FOLFIRI as firstline therapy improves survival in patients with KRAS wildtype mCRC. BRAF tumor mutation is an indicator of poor prognosis. |