Safety of VEGF-targeted tyrosine kinase inhibitors in patients (Pts) with metastatic renal cell carcinoma (mRCC) and central nervous system (CNS) metastases

Abstract

5047 Background: Hemorrhagic complications have been reported in pts treated with various angiogenesis inhibitors, however, reports of intracranial bleeding are rare. Intracranial hemorrhage has been reported during therapy with multitargeted tyrosine kinase inhibitors (TKIs) at higher dose levels during phase I evaluation. Given the occurrence of CNS metastases in RCC and the common use of TKIs, a review of the safety of TKIs in RCC pts with CNS metastases was undertaken. Methods: All pts with mRCC and CNS metastases who were treated with TKIs at the Cleveland Clinic Taussig Cancer Center were investigated. Results: Between 8/2005 and 10/2006, 23 pts with mRCC and CNS metastases were treated utilizing either sunitinib or sorafenib. 7/23 pts received sequential therapy with both TKIs. The median time to development of CNS metastases was 16.0 months (range: 0 - 288 months). Thirteen pts received sunitinib (50 mg daily, 4 out of 6 weeks) and 10 pts received sorafenib (400 mg BID continuously). All 23 pts had known CNS lesions at initiation of TKI treatment and had received prior therapy to the CNS. This consisted of either surgery and whole brain radiation therapy (WBRT; 4pts), WBRT alone (3 pts), conformal radiotherapy in the form or gamma knife or Intensity Modulated Radiation Therapy (13 pts), WBRT and gamma knife (2 pts) or surgical resection alone (1 pt). The median TKI treatment duration (including sequential TKI therapy), was 5.6 months (range: 0.3–20.3 months). No evidence of CNS intratumoral bleeding or other hemorrhagic complications have been observed. Three pts developed new metastatic foci in the brain while on sunitinib. Overall, the median time to progression was 6.5 months (0.9 - 20.3 months). Conclusions: These data suggest sunitinib or sorafenib can be safely administered to RCC pts with previously treated CNS metastases The safety of these agents in patients with untreated CNS lesions is unclear, and therefore pretreatment CNS imaging should be considered. [Table: see text]