Paul Ruff1, Eric Van Cutsem2, Radek Lakomy3, Jana Prausova4, Guy A van Hazel5, Vladimir M Moiseyenko6, Karen Soussan-Lazard7, Emmanuelle Dochy8, Emmanuelle Magherini7, Teresa Macarulla9, Demetris Papamichael10. 1. University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa. Electronic address: pruff@iafrica.com. 2. University Hospitals Leuven and KU Leuven, Belgium. 3. Masaryk Memorial Cancer Institute, Brno, Czech Republic. 4. University Hospital Motol, Prague, Czech Republic. 5. University of Western Australia, Western Australia, Australia. 6. Cancer Center, St-Petersburg, Russian Federation. 7. Sanofi, Vitry-sur-Seine, France. 8. Sanofi, Diegem, Belgium. 9. Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain. 10. Bank of Cyprus Oncology Centre, Nicosia, Cyprus.
Abstract
OBJECTIVES:Aflibercept (ziv-aflibercept) significantly improves progression-free (PFS) and overall survival (OS) when added to 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), compared with FOLFIRI alone, in patients with metastatic colorectal cancer previously treated with oxaliplatin-based therapy. This subset analysis of the VELOUR study investigates aflibercept plus FOLFIRI versus placebo plus FOLFIRI according to age. METHODS:Efficacy and safety were analyzed by treatment arm and age (≥ or <65years). RESULTS: Overall, 443 patients were ≥65years old (205 in aflibercept arm; 238 in placebo arm) and 783 were <65years old (407 in aflibercept arm; 376 in placebo arm). Median OS was 12.6 versus 11.3months (hazard ratio [HR]: 0.85; 95.34% CI 0.68-1.07) in patients ≥65years old and 14.5 versus 12.5months (HR: 0.80; 95.34% CI 0.67-0.95) in those patients <65years old, for patients receiving FOLFIRI plus aflibercept or placebo, respectively. There was no interaction between treatment and age. Treatment-emergent adverse events (AEs) were comparable for patients <65years and ≥65years old. The incidence of grade 3/4 AEs was higher for patients ≥65years old than for those <65years old in both the aflibercept (89.3% versus 80.5%) and placebo (67.4% versus 59.4%) arms. Interaction tests for grade 3/4 antiangiogenic agent-related AEs suggested no heterogeneity between the older and younger patient populations (p>0.1). CONCLUSION: A limited but consistent benefit on both OS and PFS was associated with the addition of aflibercept to FOLFIRI compared with placebo in patients <65 and ≥65years old, with a marked but manageable increase in the toxicity profile in older patients. TRIAL REGISTRATION: clinicaltrials.govNCT00561470.
RCT Entities:
OBJECTIVES: Aflibercept (ziv-aflibercept) significantly improves progression-free (PFS) and overall survival (OS) when added to 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), compared with FOLFIRI alone, in patients with metastatic colorectal cancer previously treated with oxaliplatin-based therapy. This subset analysis of the VELOUR study investigates aflibercept plus FOLFIRI versus placebo plus FOLFIRI according to age. METHODS: Efficacy and safety were analyzed by treatment arm and age (≥ or <65years). RESULTS: Overall, 443 patients were ≥65years old (205 in aflibercept arm; 238 in placebo arm) and 783 were <65years old (407 in aflibercept arm; 376 in placebo arm). Median OS was 12.6 versus 11.3months (hazard ratio [HR]: 0.85; 95.34% CI 0.68-1.07) in patients ≥65years old and 14.5 versus 12.5months (HR: 0.80; 95.34% CI 0.67-0.95) in those patients <65years old, for patients receiving FOLFIRI plus aflibercept or placebo, respectively. There was no interaction between treatment and age. Treatment-emergent adverse events (AEs) were comparable for patients <65years and ≥65years old. The incidence of grade 3/4 AEs was higher for patients ≥65years old than for those <65years old in both the aflibercept (89.3% versus 80.5%) and placebo (67.4% versus 59.4%) arms. Interaction tests for grade 3/4 antiangiogenic agent-related AEs suggested no heterogeneity between the older and younger patient populations (p>0.1). CONCLUSION: A limited but consistent benefit on both OS and PFS was associated with the addition of aflibercept to FOLFIRI compared with placebo in patients <65 and ≥65years old, with a marked but manageable increase in the toxicity profile in older patients. TRIAL REGISTRATION: clinicaltrials.govNCT00561470.
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