Pazopanib in Treatment of von Hippel-Lindau Disease


Key Points

  • The overall response rate with pazopanib was 42%.
  • By lesion, responses were seen in 52% of renal cell carcinomas, 53% of pancreatic lesions, and 4% of CNS hemangioblastomas.

In a single-center phase II trial reported in The Lancet Oncology, Jonasch et al found evidence of activity of pazopanib in the treatment of patients with von Hippel-Lindau disease.

Study Details

The study involved 31 eligible adult patients with clinical manifestations of von Hippel-Lindau disease treated at The University of Texas MD Anderson Cancer Center between January 2012 and August 2016 with pazopanib at 800 mg orally daily for 24 weeks; treatment could be continued at patient and physician discretion. Objective responses were measured for each patient and each lesion type. Radiographic assessments were performed at baseline and every 12 weeks throughout the study.


Median follow-up was 12 months. Seven patients (23%) elected to stay on the treatment after 24 weeks. Objective response (all partial responses) was observed in 13 of 31 patients (42%), with the remaining 18 patients having stable disease as best response. According to lesion site, response was observed in 31 of 59 renal cell carcinomas (52%), 9 of 17 pancreatic lesions (53%), and 2 of 49 central nervous system (CNS) hemangioblastomas (4%). Median shrinkage was 40.5% in renal lesions, 30.5% in pancreatic lesions, and 13% in hemangioblastomas.


Grade 3 or 4 transaminitis resulted in study withdrawal of 4 patients (13%), and 3 (10%) discontinued treatment due to intolerance with multiple intercurrent grade 1 and 2 toxicities. Treatment-related serious adverse events included appendicitis in one patient and gastritis in one patient. One patient had a fatal CNS bleed.

The investigators concluded, “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.”

The study was funded by Novartis and a National Cancer Institute grant.

Eric Jonasch, MD, of the Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.