| General information |
| Database: | DB00292 |
| 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: | NCT00154102 |
| 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: | an age of 18 years or older, histologically confirmed adenocarcinoma of the colon or rectum, first occurrence of metastatic disease that could not be resected for curative purposes, immunohistochemical evidence of tumor EGFR expression, ECOG performance status score of 2 or less, and adequate hematologic, hepatic, and renal function. |
| Biomarker: | epidermal growth factor receptorpositive; mutation status of the KRAS gene in tumors; BRAF mutation status (V600E) |
| Biomark Analysis: | 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: | On day 1 of a 14day treatment cycle, patients received cetuximab (initial dose 400 mg/m2 infused over 2 hours, and 250 mg/m2 weekly, over 1 hour, thereafter) followed after 1 hour by FOLFIRI (irinotecan 180 mg/m2, day 1, infused over 30 to 90 minutes, followed by leucovorin 200 mg/m2 lform, or 400 mg/m2 racemic, infused over 2 hours, followed by fluorouracil, as a 400 mg/m2 intravenous bolus then a 2, 400mg/m2 46hour continuous infusion) or FOLFIRI alone, until disease progression or the occurrence of unacceptable toxicity. |
| 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. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. |
| 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), compared with FOLFIRI alone. |
| 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), compared with FOLFIRI alone. |
| 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. |