medwireNews: Phase II study data suggest that multiple von Hippel-Lindau disease manifestations may respond to systemic treatment with pazopanib, with no unexpected side effects.
The researchers describe their preliminary findings as “encouraging” and say that 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.”
Eric Jonasch and colleagues from The University of Texas MD Anderson Cancer Center in Houston, USA, explain that there is currently no systemic therapy approved for the treatment of von Hippel-Lindau disease, an autosomal dominant hereditary cancer syndrome with pleiotropic organ manifestations.
They add that the goal of systemic therapy in these patients “is to decrease the need for surgical intervention […] by manipulating the underlying molecular mechanism that affects multi-organ manifestations.”
For the current trial, 31 adults (median age 38 years) with genetically confirmed or clinical features consistent with von Hippel-Lindau disease were treated with oral pazopanib 800 mg/day for 24 weeks.
Of these, 42% achieved an objective response, all of which were partial, according to RECIST criteria. The remaining 58% had stable disease, with no patients experiencing either a complete response or progressive disease.
Since von Hippel-Lindau disease affects multiple organs, the researchers also measured response by lesion site. They found that the response rate was 52% for the 59 renal cell carcinomas, 53% for the 17 pancreatic lesions, and 4% for the 49 central nervous system (CNS) hemangioblastomas studied.
The median time to response was 3 months for renal cell carcinoma and 6 months for both pancreatic lesions and hemangioblastomas, while median lesion shrinkage was 40.5%, 30.5%, and 13.0%, respectively.
The side-effects of pazopanib were “largely consistent with those seen in phase 3 clinical trials of pazopanib in patients with metastatic renal cell carcinoma,” Jonasch et al remark.
Four patients withdrew from the study due to grade 3 or 4 transaminitis, and three discontinued because of general intolerance to pazopanib with multiple overlapping grade 1 and 2 toxicities.
Serious adverse events related to treatment included one case each of gastritis and appendicitis. In addition, one patient with advanced, inoperable hemangioblastomas had a fall that triggered a fatal CNS bleed, which the researchers believe pazopanib could have contributed to.
Just under a quarter (23%) of the study participants chose to continue pazopanib treatment after the end of the study period.
Writing in The Lancet Oncology, Jonasch et al conclude that their findings “are potentially practice-changing for patients with von Hippel-Lindau disease because they provide an alternative approach to surgical intervention in the management of growing lesions.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group