| General information |
| Database: | DB00024 |
| Objective: | The AIO KRK0306 trial compares the efficacy of infusional 5fluorouracil, folinic acid, irinotecan (FOLFIRI) plus cetuximab with FOLFIRI plus bevacizumab in firstline treatment of metastatic colorectal cancer (mCRC). In October 2008, an amendment terminated the inclusion of patients with KRASmutated tumours. This subgroup of patients is evaluated in the present analysis, while the study is ongoing for patients with KRAS wildtype tumours. |
| Authors: | Stintzing S, et al |
| Title: | FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as firstline treatment for patients with metastatic colorectal cancersubgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK0306. |
| Journal: | Ann Oncol. |
| Year: | 2012 |
| PMID: | 22219013 |
| 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: | FOLFIRI (Tournig+ regimen)+cetuximab |
| Study Type: | a randomised German AIO study KRK0III06 |
| Key Patients Feature: | patients with metastatic colorectal cancersubgroup with KRAS |
| Biomarker: | KRAS mutation |
| Biomark Analysis: | In the present evaluation of patients with KRASmutated tumours, neither strategy demonstrated a clearly superior outcome. |
| Control Group Info: | FOLFIRI plus bevacizumab |
| Treatment Info: | patients were randomly assigned to FOLFIRI (Tournigand regimen) every 2 weeks plus cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly=arm A) or bevacizumab (5 mg/kg every 2 weeks=arm B). Among 336 randomised patients, KRAS mutation was demonstrated in 100 assessable patients. |
| Primary End Point: | objective response rate (ORR). |
| Secondary End Point: | NA |
| Patients Number: | 336 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response rate in the population treated according to protocol was 44% [95% confidence interval (CI) 29% to 59%] in the FOLFIRI plus cetuximab group and 48% (95% CI 33% to 62%) in the FOLFIRI plus bevacizumab group |
| Disease Control Rate: | DCR reached 90% (95% CI 81% to 99%) in arm A compared with 89% (95% CI 80% to 98%) in arm B |
| Median Time to Progression: | Median time to remission was short in both arms (arm A: 2.8 versus arm B: 2.9 months). |
| Median PFS A vs. C: | Median PFS was 7.5 months in arm A compared with 8.9 months in arm B [hazard ratio (HR) = 1.0]. |
| Median OS A vs. C: | Median OS was 22.7 months in arm A, while it was 18.7 months in arm B (HR = 0.86) |
| Adverse Event(agent arm): | There were no major imbalances regarding grade 3/4 haematological toxic effects between the two treatment arms. In particular, no gastrointestinal perforation could be observed in any arm. As expected, cetuximab (arm A) induced a significantly higher rate of acneiform exanthema (20% versus 0%, P< 0.001). By contrast, grade 3/4 hypertension was diagnosed more frequently in patients receiving bevacizumab (22% versus 8%, P= 0.082). |
| Conclusions: | This is the first head to head comparison of cetuximab versus bevacizumab in firstline treatment of mCRC. In the present evaluation of patients with KRASmutated tumours, neither strategy demonstrated a clearly superior outcome. |