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. Trial Registration clinicaltrials.gov NCT00561470