| General information |
| Database: | DB00306 |
| Objective: | The antiangiogenic agent aflibercept (zivaflibercept in the United States) in combination with 5fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatinbased regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. |
| Authors: | Tabernero J, et al |
| Title: | Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24140268 |
| Trial Design |
| Clinical Trial Id: | NCT00561470 |
| Agent: | aflibercept
|
| Target: | VEGFA, vascular endothelial growth factor B, PIGF
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Aflibercept+ fluorouracil, leucovorin + irinotecan (FOLFIRI) |
| Study Type: | a prospective multinational, randomised, doubleblind, parallelarm, phase III study |
| Key Patients Feature: | Eligible patients had histologically or cytologicallyproven colorectal adenocarcinoma with metastatic disease not amenable to potentially curative treatment. patients were required to have undergone a single prior oxaliplatincontaining chemotherapy regimen for metastatic disease, with documented evidence of disease progression during or after treatment completion |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo+ FOLFIRI |
| Treatment Info: | Eligible patients were randomised 1:1 to receive FOLFIRI plus either aflibercept 4 mg/kg (aflibercept arm) or placebo (control arm) every 2 weeks, with stratification according to prior bevacizumab treatment (yes/no) and ECOG PS (0/1/2). Aflibercept or placebo was administered intravenously (IV) over 1 h on day 1 of each cycle, followed immediately by the FOLFIRI regimen (irinotecan 180 mg/m2 IV over 90 min, with leucovorin 400 mg/m2 IV over 2 h, followed by 5FU 400 mg/m2 bolus and 5FU 2400 mg/m2 continuous infusion over 46 h). Premedication with atropine and antiemetics was permitted. |
| Primary End Point: | OS |
| Secondary End Point: | PFS, objective response, and treatmentemergent adverse events (TEAEs) and laboratory abnormalities. |
| Patients Number: | 1226 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS: 6.9 (6.51-7.20)(Aflibercept/FOLFIRI) versus 4.7 (4.21-5.36)(Placebo/FOLFIRI ); there was a significantly greater benefit (at the 2sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0076 [PFS]). |
| Median OS A vs. C: | median OS: aflibercept versus placebo was 12.5 (10.815.5) versus 11.7 (9.813.8) in patients with prior bevacizumab treatment and 13.9 (12.715.6) versus 12.4 (11.213.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups; there was a significantly greater benefit (at the 2sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]). |
| Adverse Event(agent arm): | the use of aflibercept increased the chemotherapyrelated toxicities associated with FOLFIRI; there was no evidence of greater toxicity in patients previously treated with bevacizumab compared with those not previously treated with bevacizumab. Furthermore, the previous use of bevacizumab did not increase the rate of antiVEGFassociated events. |
| Conclusions: | The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin they were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment. |