Pazopanib Active in von Hippel-Lindau Disease

Patients with von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, with growing lesions may have a new treatment option in the form of the antiangiogenic therapy pazopanib, according to the results of a study published in Lancet Oncology.

A small study of pazopanib in patients with VHL showed activity of the treatment in manifestations of VHL including renal cell carcinoma (RCC), pancreatic lesions, and hemangiomas.

“Pazopanib could be considered in patients with von Hippel-Lindau disease and growing lesions who might require surgical resection in the near future, or to reduce tumor size in patients with unresectable lesions,” wrote researchers led by Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center.

There are currently no approved systemic therapies for VHL disease. Prior research looking at sunitinib and pazopanib in patients with RCC suggested a potential role for this drug class in the treatment of VHL disease.

In this phase II study, Jonasch and colleagues recruited 37 patients with either genetically confirmed VHL or clinical features consistent with VHL. Thirty-one patients were eligible for treatment with 800 mg oral pazopanib for 24 weeks. Four patients were negative for germline VHL gene testing.

Overall, 13 of 31 (42%) patients achieved an objective response after pazopanib. No patients had a complete response. More than half (52%) of target patients with RCC responded to therapy, including two patients with complete response. Similarly, 52% of pancreatic lesions responded to the treatment and two of 49 hemangioblastomas showed partial response.

All patients that tested negative for germline VHL mutations had stable disease as their best response to treatment.

The overall toxicity profile was similar to that seen in other trials of pazopanib. One patient had a fatal central nervous system bleed, another had a serious treat-related appendicitis, and one had serious treatment-related gastritis. During the trial, 13% of patients withdrew because of grade 3/4 transaminitis, while 10% withdrew because of multiple intercurrent grade 1/2 adverse events.

“This study carries the potential to reduce disease burden for patients with von Hippel-Lindau disease, particularly individuals who do not have standard treatment options available but do have a confirmed DNA diagnosis and small or no CNS (central nervous system) hemangioblastomas,” Rachel H. Giles, of University Medical Center Utrecht, Netherlands, and Sven Glasker, University Ziekenhuis Brussel, Belgium, wrote in an editorial that accompanied the article.

The researchers noted that enthusiasm for this treatment might be mitigated because of the potential risk for intracranial hemorrhage, a usually rare event in patients with VHL with CNS hemangioblastomas.

“However, in the absence of hemangioblastomas with large solid components, this trial offers exciting new options for the management of patients with von Hippel-Lindau disease,” they wrote.