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.govNCT00561470