Tolerability of Alternative Dosing Schedules for Sunitinib: A Systematic Review and Meta-Analysis

Abstract

Purpose: The standard schedule for sunitinib treatment is 4 weeks on and 2 weeks off (4/2) in first-line treatment for metastatic renal cell carcinoma (mRCC). Schedule modifications, inducting 2 weeks on and 1 week off (2/1), appear to reduce the total number of treatment-related adverse events (TRAEs) without compromising efficacy. Even though TRAEs can qualitatively differ from each other, it is not dear as to what effects a 2/1 schedule has on individual TRAEs. Materials and Methods: This meta-analysis included one randomized controlled trial (RCT) and four non-randomized controlled studies (non-RCTs) that compared the two schedules in parallel. The primary objective was to estimate risk of individual adverse events (AEs) with a sunitinib 2/1 schedule versus a 4/2 schedule. Seven representative AEs were evaluated as standard data for the RCT and as weighted pooling data of the non-RCI's. Random effects modelling with Review Manager v5.3 was used to pool study-level data using the inverse-variance of each study as the weight. Results: The five selected studies included a total of 484 patients with mRCC. Risk ratios for fatigue for a 2/1 schedule were significantly lower than those for a 4/2 schedule {0.69[95% confidence intervals (CI), 0.51, 0.95] in the RCT and 0.77 (95% CI, 0.63, 0.94) in the non-RCTs}. Other TRAEs, except diarrhea and anorexia, also tended to decrease in both sets. Efficacy outcomes were comparable between 2/1 and standard schedules. Conclusion: This meta-analysis suggests that a 2/1 schedule of sunitinib lowers the risk of fatigue and the occurrence other AEs without compromising efficacy.