Better responders within a cohort of patients from the VELOUR study derive enhanced benefit from aflibercept when combined with FOLFIRI, a post-hoc analysis of the study shows.
Ian Chau, MD
Better responders within a cohort of patients from the VELOUR study derive enhanced benefit from aflibercept when combined with FOLFIRI, a post-hoc analysis of the study shows. Findings were presented during a poster session at the ESMO 15th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
Ian Chau, MD, Royal Marsden Hospital, Sutton, United Kingdom, and colleagues reported that median overall survival (OS) in the intent-to-treat (ITT) population was 13. 50 months for aflibercept plus FOLFORI-treated patients compared with12.06 months for placebo plus FOLFORI patients (P = .0032). In the subgroup categorized as “better responders,” median OS was 16.2 months for those who received additional aflibercept compared with a median OS of 13.1 months for placebo plus FOLFIR patients. The subgroup of “better responders” constituted two-thirds of all patients in both arms of the study, the investigators noted.
“The difference in survival between treatment arms also increased over time,” the authors stated. They also noted that there was a significant improvement in progression-free survival (PFS) with aflibercept compared with placebo in both the ITT population and in the better responders subgroup. In the ITT population, mean PFS was 6.9 months in the aflibercept plus FOLFIRI arm compared with a median PFS of 4.6 months for the placebo plus FOLFIRI arm—a 25% improvement in PFS time in favor of aflibercept (hazard ratio = 0.75; P = .0007.)
In the better responders subgroup, the median PFS was 7.2 months for the aflibercept plus FOLFIRI arm versus 4.8 months for placebo plus FOLFIRI for a median difference of 2.4 months between the two treatment arms.
Median difference (months)
No prior bevacizumab
There was also no difference in median OS among VELOUR patients who had received prior bevacizumab treatment compared with those who had not (Table).
Investigators also noted that in the ITT population, the overall response rate (ORR) consisting of both complete and partial responses was 19.8% for the aflibercept plus FOLFIRI cohort compared with 11.1% for their placebo counterparts. For the better responders subgroup, the ORR was 23.7% among those who received additional aflibercept versus 11% for placebo controls.
The most commonly reported adverse events (AEs) in the aflibercept plus FOLFIRI arm were gastrointestinal-related issues. This was true for both the overall VELOUR population and for the better responders subgroup. Grade 3 and higher AEs in the aflibercept plus FOLFIRI arm included diarrhea, stomatitis, fatigue, hypertension, and neutropenia. However, the authors noted that the AEs in the better responders subgroups closely approximated those in the ITT population and were consistent with expected anti-VEGF class effects.
“The addition of aflibercept to FOLFIRI chemotherapy in patients with metastatic CRC that is resistant to or has progressed after an oxaliplatin-containing regimen resulted in clinically meaningful survival gains in the better responders subgroup,” the investigators concludes. “And these statistically significant and clinically meaningful efficacy benefits in the better responders subgroup were obtained without any compromise in safety.”
Chau I, et al. A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI. Presented at: ESMO 15th World Congress on Gastrointestinal Cancer; July 3-6, 2013; Abstract P-0196.