OBJECTIVES: Metastatic renal cell carcinoma is traditionally managed with a four-week-on, two-week-off (4/2) sunitinib (SU) dosing schedule. To reduce toxicity associated with the 4/2-schedule, alternative schedules like the two-week-on, one-week-off (2/1) schedule, have been considered. We conducted a meta-analysis to estimate the comparative effectiveness and safety of alternative and traditional SU dosing schedules. METHODS:  Articles were identified from a published systematic literature review (Guida et alRESULTS:  Seven of 13 studies identified (1 RCT and 6 observational) met the inclusion criteria. Six studies evaluated 4/2- and 4/2-to-2/1-schedules and four studies evaluated the 2/1-schedule. Relative to the 4/2-schedule, the 2/1-schedule was associated with better PFS, OS, and higher rates of response. For this comparison, no Bayesian estimates were statistically different, but a classical meta-analysis for PFS limited to the 4/2-schedule vs. the 2/1-schedule showed significance due to the homogeneity in those effects (HR: 1.35 [95% CI: 1.03, 1.79]). PFS was statistically lower in patients on the 4/2-schedule vs. the 4/2-to-2/1-schedule (HR: 2.30 [95% CrI: 1.07, 4.99]) and the odds of grade 3+ diarrhoea (OR: 5.64 [95% CrI: 1.9, 20.13]) and fatigue (OR: 4.67 [95% CrI: 1.88, 13.17]) were statistically higher. There was no statistical difference for other AEs. There was insufficient evidence to address observed heterogeneity. CONCLUSIONS:  Our findings indicate that the alternative SU dosing schedules may have better effectiveness and safety profiles than the 4/2-schedule. The results should be interpreted with caution given data limitations.