OBJECTIVES To compare dose-reduction patterns in patients with RCC treated with FDA-approved tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib METHODS A retrospective analysis was conducted using data from a claims-based database (MarketScan MedStat) covering ≥18 million lives for 2002-2008 in all US census regions. Patients with ≥2 claims for RCC (ICD9 189.0 or 198.0), continuous health care coverage, >180 days' coverage before RCC diagnosis, and no claim for sorafenib or sunitinib before RCC diagnosis, who received a standard RCC initial daily dosage of sorafenib 800 mg or sunitinib 50 mg and ≥2 consecutive dispensings, were included. Initial episode was defined as time from date of first drug-dispensing to first of switch to another TKI, health care coverage end, treatment end, or March 31, 2008. Both patient and patient-time level analyses for dose reductions between treatments were conducted. RESULTS Baseline demographics between the groups (sorafenib, n=189; sunitinib, n=304) were similar except for a higher incidence of stroke (7.9% vs. 3.6%, P=.037) and other cancer site (93.7% vs. 87.8%, P=0.036) in the sorafenib group. Significantly more patients receiving sunitinib required dose reductions compared with sorafenib (first 3 months: 23.0% vs 4.2%; complete initial episodes: 35.5% vs 16.9%; P<0.001 for both). For all episodes, mean time to dose reduction was significantly longer for sorafenib than sunitinib (162 days vs 104 days, P=0.003). Significantly more dose reductions occurred within the first 3 months with sunitinib than sorafenib (65% vs. 25%, P<0.001). Controlling for different lengths of exposure time further confirmed that more dose reductions were observed in patients treated with sunitinib than with sorafenib (from 2-6 times greater, P<0.001). CONCLUSIONS This retrospective US claims analysis showed that significantly more dose reductions, including total number of patients and days, were required in patients who initially received sunitinib than in those who received sorafenib.