| General information |
| Database: | DB00295 |
| Objective: | Angiogenesis is an important therapeutic target in colorectal carcinoma. Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGF receptor 2. They assessed the efficacy and safety of ramucirumab versus placebo in combination with secondline FOLFIRI (leucovorin, fluorouracil, and irinotecan) for metastatic colorectal cancer in patients with disease progression during or after firstline therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. |
| Authors: | Tabernero J, et al |
| Title: | Ramucirumab versus placebo in combination with secondline FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after firstline therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, doubleblind, multicentre, phase 3 study. |
| Journal: | Lancet Oncol |
| Year: | 2015 |
| PMID: | 25877855 |
| Trial Design |
| Clinical Trial Id: | NCT01183780.ld |
| Agent: | ramucirumab
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Ramucirumab+ secondline FOLFIRI |
| Study Type: | a randomised, doubleblind, multicentre, phase III study |
| Key Patients Feature: | pts aged 18 years or older, had pathologically confirmed colorectal carcinoma, known KRAS exon 2 mutation status (mutant or wildtype) |
| Biomarker: | KRAS mutation status |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Eligible patients had disease progression during or within 6 months of the last dose of firstline therapy. patients were randomised (1:1) via a centralised, interactive voiceresponse system to receive 8 mg/kg intravenous ramucirumab plus FOLFIRI or matching placebo plus FOLFIRI every 2 weeks until disease progression, unacceptable toxic effects, or death. |
| Primary End Point: | overall survival. |
| Secondary End Point: | progression free survival; the proportion of patients who achieved an objective response; and disease control. |
| Patients Number: | 1072 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Median overall survival was 13.3 months (95% CI 12.414.5) for patients in the ramucirumab group versus 11.7 months (10.812.7) for the placebo group (hazard ratio 0.844 95% CI 0.7300.976; logrank p=0.0219). Survival benefit was consistent across subgroups of patients who received ramucirumab plus FOLFIRI. |
| Adverse Event(agent arm): | Grade 3 or worse adverse events seen in more than 5% of patients were neutropenia (203 [38%] of 529 patients in the ramucirumab group vs 123 [23%] of 528 in the placebo group, with febrile neutropenia incidence of 18 [3%] vs 13 [2%]), hypertension (59 [11%] vs 15 [3%]), diarrhoea (57 [11%] vs 51 [10%]), and fatigue (61 [12%] vs 41 [8%]). |
| Conclusions: | Ramucirumab plus FOLFIRI significantly improved overall survival compared with placebo plus FOLFIRI as secondline treatment for patients with metastatic colorectal carcinoma. No unexpected adverse events they were identified and toxic effects they were manageable. |