Observed benefit and safety of aflibercept in elderly patients with metastatic colorectal cancer: An age-based analysis from the randomized placebo-controlled phase III VELOUR trial

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 <65 years). Results: Overall, 443 patients were 65 years old (205 in aflibercept arm; 238 in placebo arm) and 783 were <65 years old (407 in aflibercept arm; 376 in placebo arm). Median OS was 12.6 versus 11.3 months (hazard ratio [HR]: 0.85; 95.34% CI 0.68-1.07) in patients >= 65 years old and 14.5 versus 12.5 months (HR: 0.80; 95.34% CI 0.67-0.95) in those patients <65 years 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 <65 years and >= 65 years old. The incidence of grade 3/4 AEs was higher for patients >= 65 years old than for those <65 years 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 >= 65 years old, with a marked but manageable increase in the toxicity profile in older patients. (C) 2017 Elsevier Ltd. All rights reserved.