BACKGROUND: No approved systemic therapy exists for von Hippel-Lindau disease, 
an autosomal dominant disorder with pleiotropic organ manifestations that 
include clear cell renal cell carcinomas; retinal, cerebellar, and spinal 
haemangioblastomas; pheochromocytomas; pancreatic serous cystadenomas; and 
pancreatic neuroendocrine tumours. We aimed to assess the activity and safety of 
pazopanib in patients with von Hippel-Lindau disease.
METHODS: In this non-randomised, single-centre, open-label, phase 2 trial, adult 
patients with clinical manifestations of von Hippel-Lindau disease were 
recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, 
USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an 
option to continue treatment if desired by the patient and treating physician. 
Primary endpoints were the proportion of patients who achieved an objective 
response and safety in the per-protocol population. The objective response was 
measured for each patient and each lesion type. Radiographic assessments were 
done at baseline and every 12 weeks throughout the study. Activity and safety 
were assessed with continuous monitoring and a Bayesian design. This study is 
registered with ClinicalTrials.gov, number NCT01436227, and is closed to 
accrual.
FINDINGS: Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with 
genetically confirmed or clinical features consistent with von Hippel-Lindau 
disease, of whom 31 eligible patients were treated with pazopanib. The 
proportion of patients who achieved an objective response was 42% (13 of 31 
patients). By lesion sites responses were observed in 31 (52%) of 59 renal cell 
carcinomas, nine (53%) of 17 pancreatic lesions, and two (4%) of 49 CNS 
haemangioblastomas. Seven (23%) of 31 patients chose to stay on the treatment 
after 24 weeks. Four (13%) of 31 patients withdrew from the study because of 
grade 3 or 4 transaminitis, and three (10%) discontinued study treatment because 
of treatment intolerance with multiple intercurrent grade 1-2 toxicities. 
Treatment-related serious adverse events included one case each of appendicitis 
and gastritis and one patient had a fatal CNS bleed.
INTERPRETATION: Pazopanib was associated with encouraging preliminary activity 
in von Hippel-Lindau disease, with a side-effect profile consistent with that 
seen in previous trials. Pazopanib could be considered as a treatment choice for 
patients with von Hippel-Lindau disease and growing lesions, or to reduce the 
size of unresectable lesions in these patients. The safety and activity of 
pazopanib in this setting warrants further investigation.
FUNDING: Novartis Inc and NIH National Cancer Institute core grant.