The survival benefit demonstrated in the VELOUR study for FOLFIRI (irinotecan, fluorouracil [5-FU], leucovorin) plus ziv-aflibercept (Zaltrap) vs FOLFIRI plus placebo in metastatic colorectal cancer patients who progressed on oxaliplatin-based chemotherapy persisted beyond median survival times for some patients. This “suggested subpopulations might have different magnitudes of survival gain,” Ian Chau, MD, of the Royal Marsden Hospital in London, and colleagues noted in BMC Cancer.
To determine which patients received the greatest benefit from FOLFIRI with ziv-aflibercept, the investigators conducted a posthoc multivariate analysis of the VELOUR intent-to-treat population. The posthoc subset–the better-efficacy subgroup—excluded the 124 patients (approximately 10%) who had recurrence within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers).
The better-efficacy subgroup included 404 patients (66%) from the FOLFIRI/ziv-alflibercept investigational arm of the VELOUR trial and 406 patients (66%) from the ziv-alflibercept/placebo investigational arm. All had performance status of 0 with any number of metastatic sites or performance status of 1 with more than two metastatic sites.
Survival Outcomes
“A significant improvement in efficacy outcome was observed with [ziv-]aflibercept in this better efficacy subgroup,” the authors wrote. Median overall survival for patients receiving FOLFIRI/ziv-aflibercept was 16.2 months vs 13.1 months for patients receiving FOLFIRI/placebo (adjusted hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.61–0.86). “Over time, the magnitude of survival differences between the 2 treatment groups continued to increase in the better efficacy subgroup with the absolute [overall survival] rate differences increased from 5% at 6 months to 15% at 30 months,” the researchers added.
A significant improvement was also observed for progression free survival. Median progression-free survival was 7.2 months in the FOLFIRI/ziv-aflibercept group vs 4.8 months in the FOLFIRI/placebo group. “The absolute difference in 6-month [progression-free survival] rates was 25%,” the researchers reported. Objective response rates were 23.7% with ziv-aflibercept vs 11% with placebo.
No benefit was derived from ziv-aflibercept for patients in the poorer-efficacy subgroup, which was comprised of adjuvant fast relapsers or patients with performance status of 2 or performance status of 1 with two or more metastatic sites. For these patients, median overall survival was 10.4 months for FOLFIRI/ziv-aflibercept and 9.6 months for FOLFIRI/placebo (adjusted HR = 0.97, 95% CI = 0.78–1.21). No improvements were observed for progression-free survival or overall response rate in this subgroup.
“The efficacy outcome benefits in the better efficacy subgroup were obtained without any compromise to safety,” the investigators stated. Adverse events “in the better efficacy subgroup closely mirrored those in the overall safety population. The toxicity profile is in line with expectations for the anti-VEGF plus chemotherapy class effect seen in other studies.”
The authors concluded that identifying prognostic criteria for second-line patients with metastatic colorectal cancer “may help to guide practitioners toward targeted use of biologicals for maximal survival gains in clinically relevant patient populations.” ■
Chau I, et al: BMC Cancer, 14:605, 2014.
