Tyrosine kinase inhibitors and development of brain metastasis in metastatic renal cell carcinoma: A retrospective review.

Abstract

340 Background: Tyrosine kinase inhibitors (TKIs) have been shown to improve overall survival (OS) in metastatic renal cell carcinoma (mRCC) but their effect on brain metastasis (BM) development is unclear. The purpose of our study is to evaluate the impact of TKIs on incidence of BM and OS in patients with mRCC. Methods: Searched the M. D. Anderson Cancer Center (MDACC) tumor registry for patients who presented with mRCC in 2002-2003 and 2006-2007 with no BM at initial staging. The following items were retrospectively collected: age, sex, Fuhrman grade, sites of disease, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), MSKCC risk category, BM treatment, and vital status. Interaction between OS and incidence of BM and these variables was estimated using the Cox proportional hazards model. OS and incidence of BM were estimated using the Kaplan-Meier (K-M) method. Results: 338 patients were identified; 154 (46%) were treated with a TKI prior to BM, and 184 (54%) were not. There were no significant differences in age, histology, involved sites of disease other than lung, nephrectomy, or MSKCC risk category between the groups. A higher proportion of the nonTKI group received other systemic agents and had lung metastasis at initial staging (p=0.03). Median OS was longer in the TKI-treated group (25 months versus 12.1 months, p<0.0001). In Cox multivariate analysis, TKI treatment (HR=0.53, 95% CI 0.38-0.74, p<0.001) was associated with improved OS and lung/mediastinal involvement and ECOG performance status > 2 (HR 1.87, 95% CI 1.28-2.71, p=0.001) were associated with poor OS. Median OS after BM was not significantly different between TKI treated and untreated groups. 44 patients (13%) developed a BM, including 29 (15.8%) of the nonTKI group and 15 (9.7%) of the TKI group. In K-M analysis, the 5-year incidence of BM was 40% versus 17% respectively (logrank p<0.001). In Cox multivariate analysis, TKI treatment was associated with lower incidence of BM (HR=0.39, 95% CI 0.21-0.73, p=0.003). Lung metastasis increased the risk of BM (HR=9.61, 95% CI 2.97-31.1, p<0.001). Conclusions: Treatment with TKI agents reduces the incidence of BM in mRCC. Lung metastasis is a risk factor for BM development. No significant financial relationships to disclose.