Alternate sunitinib schedules attracted the interest of oncologists recently owing to their superior safety profile. This meta-analysis compared the tolerability and efficacy of a new alternative dosing schedule (2 weeks on/1 week off) of sunitinib with the traditional 4/2 schedule in patients with metastatic renal cell carcinoma (mRCC). Studies were retrieved from Medline, Cochrane Central, Scopus, Embase, and Web of Science databases. Data were extracted and pooled as hazard ratio (HR: survival data) or odds ratio (OR: dichotomous data) using Comprehensive Meta-analysis software. Based on data of 1173 patients, the progression-free survival (HR, 0.52; 95% confidence interval [CI], 0.39-0.95; P < .0001), overall survival (HR, 0.6; 95% CI, 0.43-0.85; P < .0001), and stable disease rates (OR, 0.38; 95% CI, 0.19-0.76; P = .006) were significantly improved on the alternative 2/1 schedule, compared with the traditional 4/2 schedule. However, the complete response (OR, 1.32; 95% CI, 0.34-5.22; P = .69) and partial response (OR, 1.34; 95% CI, 0.44-4.14; P = .61) rates were comparable between the 2 regimens. The tolerability of the alternative 2/1 schedule was superior to the traditional one as investigated adverse events like fatigue (OR, 2.91; 95% CI, 1.89-4.46; P < .0001), hypertension (OR, 2.08; 95% CI, 1.56-2.75; P < .0001), and diarrhea (OR, 2.18; 95% CI, 1.19-3.98; P = .012) were significantly less common. In conclusion, the alternative 2/1 sunitinib schedule provides improved tolerability and survival in patients with mRCC. Large randomized trials with long follow-up periods are required to validate and confirm these findings. (C) 2019 Elsevier Inc. All rights reserved.