Benefit-risk evaluation of ziv-aflibercept in combination with irinotecan-fluoropyrimidine-based chemotherapy (FOLFIRI) from the VELOUR trial using multicriteria decision analysis (MCDA).

Abstract

e14656 Background: In the VELOUR trial, in metastatic colorectal cancer (mCRC) patients, ziv-aflibercept (Afl) combined with FOLFIRI demonstrated significant improvements in median overall survival (OS) by 1.44 mos and median progression-free survival (PFS) by 2.23 mos when compared with FOLFIRI + placebo. We utilized a systematic approach to evaluate the benefit/risk profile of the regimen in the target disease population. Objectives: To evaluate favorable and unfavorable effects of Afl in combination with FOLFIRI in patients with mCRC previously treated with an oxaliplatin-based regimen using the MCDA method. Methods: Data from VELOUR were used to compare the 2 treatment arms (Afl + FOLFIRI vs placebo + FOLFIRI). An 8-step process based on the MCDA was used to construct a value tree that displayed evaluation criteria for favorable and unfavorable effects, determined score, assigned weight for each criteria, and then combined weights and scores for each treatment arm to derive an overall value. Sensitivity analysis was also conducted. Results: The final value tree comparing the 2 treatment arms had 2 branches representing favorable and unfavorable effects. Favorable effects criteria included survival probability at 12, 18, and 24 mos, median OS, median PFS, and overall response rate. Unfavorable effects criteria included 11 anti-VEGF- and FOLFIRI-associated adverse events (AEs), as well as deaths and treatment discontinuation due to AEs. The survival rate at 24 mos had the highest weight (100), followed by median OS (95). For unfavorable effects, diarrhea had the highest weight (15), followed by arterial thromboembolism (ATE) (12). AEs seen with Afl + FOLFIRI were generally manageable; their clinical impact did not outweigh the benefits. The overall value combining favorable and unfavorable effects for Afl + FOLFIRI was 53 vs 40 for placebo + FOLFIRI. Conclusions: Results from this quantitative benefit-risk analysis indicate that the benefit-risk balance for ziv-aflibercept in combination with FOLFIRI is favorable compared with FOLFIRI alone in adults with mCRC previously treated with an oxaliplatin-based regimen. Clinical trial information: NCT00561470.