| General information |
| Database: | DB00291 |
| Objective: | They investigated the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as firstline treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab. |
| Authors: | Van Cutsem E, et al |
| Title: | Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. |
| Journal: | N Engl J Med |
| Year: | 2009 |
| PMID: | 19339720 |
| 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+ chemotherapy |
| Study Type: | a randomized, openlabel, multicenter 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: | mutation status of the KRAS gene in tumors |
| Biomark Analysis: | There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) but not for progression free survival (P=0.07) or overall survival (P=0.44). The hazard ratio for progression free survival among patients with wildtypeKRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximabFOLFIRI group. |
| Control Group Info: | FOLFIRI alone |
| Treatment Info: | On day 1 of each 14day period during the study, patients in the FOLFIRI group received a 30 to 90minute infusion of irinotecan at a dose of 180 mg per square meter of bodysurface area; an infusion, for 120 minutes, of racemic leucovorin or Lleucovorin at a dose of 400 or 200 mg, respectively, per square meter of bodysurface area; fluorouracil in a bolus of 400 mg per square meter of bodysurface area and then continuous infusion for 46 hours of 2400 mg per square meter of bodysurface area. |
| Primary End Point: | progression free surviva. |
| Secondary End Point: | the overall survival time, the rate of best overall response, and safety end points. |
| Patients Number: | 1198 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | There was a significant interaction between treatment group and KRAS mutation status for tumor response (P=0.03) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The hazard ratio for progression free survival in the cetuximabFOLFIRI group as compared with the FOLFIRI group was 0.85 (95% confidence interval [CI], 0.72 to 0.99; P=0.048). There was no significant interaction between treatment group and KRAS mutation status for progression free survival (P=0.07). The hazard ratio for progression free survival among patients with wildtypeKRAS tumors was 0.68 (95% CI, 0.50 to 0.94), in favor of the cetuximabFOLFIRI group. |
| Median OS A vs. C: | There was no significant difference in the overall survival between the two treatment groups (hazard ratio, 0.93; 95% CI, 0.81 to 1.07; P=0.31). There was no significant interaction between treatment group and KRAS mutation status for overall survival (P=0.44). |
| Adverse Event(agent arm): | The following grade 3 or 4 adverse events were more frequent with cetuximab plus FOLFIRI than with FOLFIRI alone: skin reactions (which were grade 3 only) (in 19.7% vs. 0.2% of patients, P<0.001), infusionrelated reactions (in 2.5% vs. 0%, P<0.001), and diarrhea (in 15.7% vs. 10.5%, P=0.008). |
| Conclusions: | Firstline treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer. The benefit of cetuximab was limited to patients with KRAS wildtype tumors. |