Survival outcomes associated with different sunitinib dosing regimens in metastatic renal cell carcinoma.

Abstract

Standard dosing regimen of sunitinib for metastatic renal cell carcinoma consists of four weeks treatment followed by two weeks rest (intermittent dosing). Alternative regimens have been suggested, including continuous daily dosing (continuous dosing) and non-conventional dosing (non-conventional dosing: e.g. two weeks on/one week off, non-conventional dosing), to provide more individualized therapy with less toxicities. It is unclear whether non-standard sunitinib dosing affects survival outcomes. Metastatic renal cell carcinoma patients treated with sunitinib between 1 July 2007 and 1 July 2011 at our institution. Medical records and dispensing data were reviewed retrospectively to categorize sunitinib dosing as intermittent dosing, continuous dosing, or non-conventional dosing. Primary outcome was to compare overall survival associated with varying regimens, with secondary outcomes of progression-free survival and incidence of treatment discontinuation due to adverse effects. A total of 180 patients were identified. Most patients received intermittent dosing (n = 120, 67%), followed by continuous dosing (n = 32, 18%) and non-conventional dosing (n = 28, 16%). Compared to intermittent dosing, continuous dosing was associated with similar overall survival (median 9 vs. 13 months, HR 0.67, 95% CI: 0.43-1.06, p = 0.088) while non-conventional dosing was associated with significantly longer overall survival (median 9 vs. 23 months, HR 0.55, 95% CI: 0.34-0.90, p = 0.016). Progression-free survival was significantly better for continuous dosing (median 4 vs. 9 months, HR 0.61, 95% CI: 0.40-0.94, p = 0.025) and non-conventional dosing (median 4 vs. 10 months, HR 0.61, 95% CI: 0.39-0.95, p = 0.03) when compared to intermittent dosing. Similar to prior sunitinib trials, a significant proportion of patients (20%) discontinued sunitinib therapy due to adverse effects. Based on retrospective, real-world data, alternative sunitinib dosing regimens appear to be viable options for patients with metastatic renal cell carcinoma.