| General information |
| Database: | DB00017 |
| Objective: | Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidinebased chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. They studied the effect of adding the novel antiangiogenic agent aflibercept (also known as zivaflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. |
| Authors: | Van Cutsem E, et al |
| Title: | Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatinbased regimen. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22949147 |
| Trial Design |
| Clinical Trial Id: | NCT00561470 |
| Agent: | aflibercept
|
| Target: | VEGFA, vascular endothelial growth factor B, PIGF
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | colorectal adenocarcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | FOLFIRI+aflibercept |
| Study Type: | a prospective multinational, randomized, doubleblind, parallelarm, phase III study |
| Key Patients Feature: | Eligible patients had histologically or cytologically proven colorectal adenocarcinoma with metastatic disease not amenable to potentially curative treatment.Patients who experienced relapse within 6 months of completion of oxaliplatinbased adjuvant therapy were eligible |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo in combination with FOLFIRI |
| Treatment Info: | patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. |
| Primary End Point: | overall survival (OS), PFS was a secondary efficacy end point. |
| Secondary End Point: | Additional secondary end points included objective response (complete response and partial response) and treatmentemergent adverse events and laboratory abnormalities. |
| Patients Number: | 1226 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.90 versus 4.67 months (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001) |
| Median OS A vs. C: | 13.50 versus 12.06 months (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) |
| Adverse Event(agent arm): | Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic antivascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapyrelated toxicities. |
| Conclusions: | Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin. |