Jonasch E, et al. - Researchers tested pazopanib in patients with von Hippel-Lindau disease, focusing on its activity and safety. According to findings, encouraging preliminary activity and a side-effect profile consistent with that seen in previous trials was seen with pazopanib use in patients with clinical manifestations of von Hippel-Lindau disease. For patients with von Hippel-Lindau disease and growing lesions and for reducing the size of unresectable lesions in these patients, pazopanib could be an appropriate treatment option.

Methods

• This is a non-randomized, single-center, open-label, phase 2 trial.
• From the University of Texas MD Anderson Cancer Center (Houston, TX, US), adult patients with clinical manifestations of von Hippel-Lindau disease were recruited for this trial.
• These patients were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if the patient and treating physician wanted to.
• Researchers assessed the proportion of patients who achieved an objective response and safety in the per-protocol population (primary endpoints).
• They measured objective response for each patient and each lesion type.
• They also performed radiographic assessments at baseline and every 12 weeks throughout the study.
• With continuous monitoring and a Bayesian design, they evaluated activity and safety.

Results

• A total of 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease were screened between January 18, 2012 and August 10, 2016, of whom 31 eligible patients received treatment with pazopanib.
• An objective response was seen in 42% patients (13 of 31 patients).
• By lesion site, 31 (52%) of 59 renal cell carcinomas, nine (53%) of 17 pancreatic lesions, and two (4%) of 49 CNS hemangioblastomas responded.
• Continuing the treatment after 24 weeks was chosen by 7 (23%) of 31 patients.
• Grade 3 or 4 transaminitis led 4 (13%) of 31 patients to withdraw from the study.
• Treatment intolerance with multiple intercurrent grade 1–2 toxicities accounted for study treatment discontinuation by three (10%) patients.
• One case each of appendicitis and gastritis and one of fatal CNS bleed were reported as treatment-related serious adverse events.