Observed Benefit of Aflibercept in MCRC Patients ≥65 Years Old: Results of a Prespecified Age-Based Analysis of the Velour Study

Abstract

Background: The VELOUR study demonstrated a statistically significant and clinically meaningful survival benefit for aflibercept (ziv‐aflibercept in the United States) plus FOLFIRI (5‐fluorouracil‐leucovorin‐irinotecan) versus placebo + FOLFIRI in patients with metastatic colorectal cancer who had progressed following oxaliplatin therapy (Van Cutsem E et al. J Clin Oncol. 2012;30:3499‐3506). Methods: This prespecified analysis compared the efficacy and safety of aflibercept + FOLFIRI with placebo + FOLFIRI in patients with metastatic colorectal cancer older than 65 years. Overall survival, progression‐free survival, and incidence of grade 3/4 adverse events were analyzed. Results: Of the 1226 randomized patients in the VELOUR study, 438 patients (36%) were aged >65 years (205 in the aflibercept + FOLFIRI arm and 233 in the placebo + FOLFIRI arm). Overall survival was 12.6 months and 11.3 months in the aflibercept and placebo arms, respectively, in this elderly subset (HR = 0.853; 95% CI: 0.682‐1.066). Median progression‐free survival was also greater in the aflibercept arm (6.6 months) than in the placebo arm (4.4 months) for patients aged >65 years (HR = 0.748, 95% CI: 0.598‐0.936). All tests for interaction of grade 3/4 VEGF‐related adverse events (eg, fistula, hemorrhage, hypertension, proteinuria) had P > 0.1, suggesting no evidence of heterogeneity. Interaction tests for grade 3/4 chemotherapy‐related adverse events (eg, asthenia, dehydration, diarrhea, infections, neutropenia and neutropenic complications, stomatitis) demonstrated only an interaction between age and the occurrence of dehydration (P = 0.0058). Conclusion: Taken together, in this prespecified analysis of the VELOUR trial, an improvement in progression‐free survival was observed in the aflibercept + FOLFIRI arm; the data also suggested a trend towards improved overall survival in older patients with metastatic colorectal cancer. With the exception of dehydration, the safety profile of aflibercept + FOLIRI in older patients with metastatic colorectal cancer was similar to the safety profile in the overall VELOUR trial and consistent with adverse events routinely managed by clinicians working in oncology.