BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as 
a mediator of resistance to anti-vascular endothelial growth factor (VEGF) 
therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in 
patients progressing on anti-VEGF treatment.
METHODS: Patients with measurable advanced colorectal or non-small cell lung 
cancer with progression despite anti-VEGF treatment within 56 days, good 
performance status and adequate organ function were eligible. A research tumor 
biopsy was followed by treatment with dovitinib 500 mg on a 5-day on/2-day off 
schedule for 28-day cycles. The primary endpoint of tumor response was evaluated 
every 2 cycles. Secondary endpoints included toxicity and 8-week disease control 
rate. Intratumor mRNA expression of angiogenic mediators was analyzed using a 
next generation sequencing based expression array.
RESULTS: Ten patients treated previously with bevacizumab or ziv-aflibercept 
enrolled. The study closed with termination of dovitinib development. No 
responses were observed in 7 evaluable patients. The best response was stable 
disease in 1 patient. Common toxicities included gastrointestinal, metabolic, 
and biochemical derangements. All patients experienced at least one grade ≥ 3 
treatment-related adverse event, most commonly fatigue, elevated GGT, and 
lymphopenia. Expression of multiple angiogenic mediators was common in tumors 
progressing on anti-VEGF therapy including high levels of FGFR1 and VEGFA.
CONCLUSIONS: We found no evidence for the activity of dovitinib in patients who 
had recently progressed on anti-VEGF therapy and toxicities were significant. In 
tumors progressing despite anti-VEGF therapy, a multitude of pro-angiogenic 
mediators are expressed, including members of the FGF pathway.