BACKGROUND: Patients with metastatic colorectal cancer (mCRC) previously-treated with oxaliplatin benefit significantly from the addition of aflibercept to FOLFIRI in relation to overall survival, progression-free survival and response rate. PATIENTS AND METHODS: The results for efficacy and safety over the time course of the VEGF Trap (aflibercept) with irinotecan in colorectal cancer after failure of oxaliplatin regimen trial were analysed based on data from 1226 patients randomised to receive FOLFIRI plus either aflibercept (n=612) or placebo (n=614). Hazard ratios (HR) by 6-month time period were estimated using a piecewise Cox proportional hazard model. Severity of adverse events (AEs) was graded using National Cancer Institute Common Terminology Criteria, version 3.0. RESULTS: The estimated probabilities of survival were 38.5% versus 30.9% at 18 months, 28.0% versus 18.7% at 24 months and 22.3% versus 12.0% at 30 months, for the aflibercept- and placebo-treated arms, respectively. The proportional improvement in the HR over time was consistent with the survival probability results; survival at 24 months was improved by 50% and almost doubled at 30 months. The majority of worst-grade AEs occurred within the first four cycles of treatment and in a small percent of treatment cycles and were mostly reversible. Common chemotherapy- and anti-vascular epithelial growth factor (VEGF)-associated AEs occurred rarely and in a small proportion of cycles with the majority being of single occurrence. CONCLUSIONS: The addition of aflibercept to FOLFIRI showed a continued and persistent improvement in overall survival over time in patients with mCRC. Although grade 3-4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation.

Amphia Hospital Breda The Netherlands

Centro De Oncologia Hospital Sirio Libanes São Paulo Brazil

Department of Medical Oncology Tumor Biology Center Freiburg Germany

Fakultni nemocnice v Motole Praha Czech Republic

Martin Luther University Halle Wittenberg Germany

Masaryk Memorial Cancer Institute Brno Czech Republic

Monash University Victoria Australia

Oncology Research Institute Na NN Petrov St Petersburg Russian Federation

Russells Hall Hospital Dudley UK

Sanofi Global Oncology Medical Affairs Cambridge MA United States

Sanofi Global Oncology Research and Development Cambridge MA United States

Sanofi Vitry sur Seine France

The Royal Marsden Hospital Sutton UK

University Hospitals Leuven and KU Leuven Belgium

University of Western Australia Western Australia Australia

University of Witwatersrand Faculty of Health Sciences Johannesburg South Africa

Vall d'Hebron University Hospital and Institute of Oncology Universitat Autònoma de Barcelona Barcelona Spain

References provided by Crossref.org

Aflibercept Plus FOLFIRI vs. Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy