| General information |
| Database: | DB00028 |
| Objective: | Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with firstline fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. They aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wildtype metastatic colorectal cancer. |
| Authors: | Heinemann V, et al |
| Title: | FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer (FIRE3): a randomised, openlabel, phase 3 trial. |
| Journal: | Lancet Oncol |
| Year: | 2014 |
| PMID: | 25088940 |
| Trial Design |
| Clinical Trial Id: | NCT00433927 |
| 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: | firstline fluorouracil, folinic acid, + irinotecan (FOLFIRI)+Cetuximab/bevacizumab |
| Study Type: | openlabel, randomised, phase III trial |
| Key Patients Feature: | patients aged 1875 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 02, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria. |
| Biomarker: | KRAS exon 2 wildtype |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | FOLFIRI+bevacizumab |
| Treatment Info: | patients were centrally randomised by fax (1:1) to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab (using permuted blocks of randomly varying size), stratified according to ECOG performance status, number of metastatic sites, white blood cell count, and alkaline phosphatase concentration. |
| Primary End Point: | objective response analysed by intention to treat. The study has completed recruitment, but followup of participants is ongoing. |
| Secondary End Point: | NA |
| Patients Number: | 592 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 184 (62.0%, 95% CI 56.267.5) patients in the cetuximab group achieved an objective response compared with 171 (58.0%, 52.163.7) in the bevacizumab group (odds ratio 1.18, 95% CI 0.851.64; p=0.18). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival was 10.0 months (95% CI 8.810.8) in the cetuximab group and 10.3 months (9.811.3) in the bevacizumab group (hazard ratio [HR] 1.06, 95% CI 0.881.26; p=0.55) |
| Median OS A vs. C: | median overall survival was 28.7 months (95% CI 24.036.6) in the cetuximab group compared with 25.0 months (22.727.6) in the bevacizumab group (HR 0.77, 95% CI 0.620.96; p=0.017). |
| Adverse Event(agent arm): | Safety profiles were consistent with the known sideeffects of the study drugs. The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (73 [25%] of 297 patients in the cetuximab group vs 62 [21%] of 295 patients in the bevacizumab group), skin reactions (77 [26%] vs six [2%]), and diarrhoea (34 [11%] vs 40 [14%]). |
| Conclusions: | Although the proportion of patients who achieved an objective response did not significantly differ bettheyen the FOLFIRI plus cetuximab and FOLFIRI plus bevacizumab groups, the association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred firstline regimen for patients with KRAS exon 2 wildtype metastatic colorectal cancer. |