BACKGROUND: An unmet medical need exists for patients with metastatic renal cell 
carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. 
Fibroblast growth factor (FGF) pathway activation has been proposed as a 
mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral 
tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore 
compared dovitinib with sorafenib as third-line targeted therapies in patients 
with metastatic renal cell carcinoma.
METHODS: In this multicentre phase 3 study, patients with clear cell metastatic 
renal cell carcinoma who received one previous VEGF-targeted therapy and one 
previous mTOR inhibitor were randomly assigned through an interactive voice and 
web response system to receive open-label dovitinib (500 mg orally according to 
a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in 
a 1:1 ratio. Randomisation was stratified by risk group and region. The primary 
endpoint was progression-free survival (PFS) assessed by masked central review. 
Efficacy was assessed in all patients who were randomly assigned and safety was 
assessed in patients who received at least one dose of study drug. This study is 
registered with ClinicalTrials.gov, number NCT01223027.
FINDINGS: 284 patients were randomly assigned to the dovitinib group and 286 to 
the sorafenib group. Median follow-up was 11·3 months (IQR 7·9-14·6). Median PFS 
was 3·7 months (95% CI 3·5-3·9) in the dovitinib group and 3·6 months (3·5-3·7) 
in the sorafenib group (hazard ratio 0·86, 95% CI 0·72-1·04; one-sided p=0·063). 
280 patients in the dovitinib group and 284 in the sorafenib group received at 
least one dose of study drug. Common grade 3 or 4 adverse events included 
hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), 
and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), 
fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia 
(18 [6%]) in the sorafenib group. The most common serious adverse event was 
dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, 
respectively).
INTERPRETATION: Dovitinib showed activity, but this was no better than that of 
sorafenib in patients with renal cell carcinoma who had progressed on previous 
VEGF-targeted therapies and mTOR inhibitors. This trial provides reference 
outcome data for future studies of targeted inhibitors in the third-line 
setting.
FUNDING: Novartis Pharmaceuticals Corporation.