The Efficacy and Safety of Tyrosine Kinase Inhibitors for Von Hippel–Lindau Disease: A Retrospective Study of 32 Patients

Abstract

Background: Von Hippel-Lindau (VHL) disease is an autosomal-dominant hereditary cancer syndrome. Currently, studies on tyrosine kinase inhibitor (TKI) therapy for VHL disease are scarce. In this study, we retrospectively evaluated the efficacy and safety of four TKIs in patients with VHL disease.Methods: Patients diagnosed with VHL disease who were receiving TKIs were recruited. Patients were treated with sunitinib (n = 12), sorafenib (n = 11), axitinib (n = 6), or pazopanib (n = 3). The therapeutic response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.Results: From July 2009 to September 2018, 32 patients with VHL disease were eligible and included in this study. The median duration of TKI therapy was 22 months (IQR 8.5–44.75), and the median follow-up period was 31.5 months (IQR 13.5–63.5). According to the RECIST, 9 (28%) of 32 patients showed a partial response, 15 (47%) achieved stable disease, and eight exhibited continued disease progression. A partial response was observed in 11 (31%) of 36 renal cell carcinomas, 4 (27%) of 15 pancreatic lesions, and 1 (20%) of five central nervous system (CNS) hemangioblastomas. The average tumor size decreased significantly for renal cell carcinomas (P = 0.0001), renal cysts (P = 0.027), and pancreatic lesions (P = 0.003) after TKI therapy. Common side effects included hand–foot skin reactions, diarrhea, alopecia, thrombocytopenia, and fatigue.Conclusions: Partial alleviation of VHL disease-related tumors can be achieved by TKI therapies in some patients, providing an alternative treatment strategy, and the side effects of TKIs are acceptable. Larger prospective studies are warranted to further evaluate the efficacy and safety of TKIs in patients with VHL disease.

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

“…Sunitinib is approved for the management of pNETs and has shown stability in 5 out of 7 cases of VHL-associated pNETs ( 150 , 151 ). Another study using multiple antiangiogenic treatments (sunitinib, sorafenib, axitinib, pazopanib) showed a partial response in 4 of the 15 VHL patients with cystic or solid pancreatic tumors ( 152 ). In a phase 2 trial, 53% of VHL pancreatic lesions responded to pazopanib (anti-VEGFR 1-3, anti-PDGFR α-β, c-KIT), but most of them were serous cystadenomas ( 153 ).…”

A case of von Hippel–Lindau disease with renal cell carcinoma treated by partial nephrectomy with pre- and post-surgical axitinib therapy

“… 2 Ma et al reported the effect of TKIs on metastatic RCC in 32 patients with VHL, recording partial response and stable disease rates of 28% and 47%, respectively, and median overall survival of 70 months. 5 …”

Management recommendations for pancreatic manifestations of von Hippel–Lindau disease

“…Tyrosine kinase inhibitors, including sunitinib, sorafenib, axitinib, and pazopanib, have been evaluated for unresectable and/or progressive VHL-related neoplasms. 64 Among those, sunitinib was evaluated in a prospective randomized controlled trial of sporadic PNETs and prolonged progression-free survival, 65 and it may be effective for the management of PNETs in patients with VHL. [66][67][68][69] Jonasch et al 70 reported the efficacy of pazopanib in treating VHL-related neoplasms in a phase 2 study, which included 17 assessed pancreatic lesions, and there was high efficacy in reducing the size of PNETs.…”