Safety and Efficacy of Targeted Therapy for Renal Cell Carcinoma With Brain Metastasis

The role of targeted therapy is not well established for patients with renal cell carcinoma and brain metastasis. In this retrospective analysis of 65 patients, the use of targeted agents in this setting was not associated with excessive neurologic adverse events. In this series, clear cell histology, favorable risk status according to the Memorial Sloan Kettering Cancer Center stratification, and solitary brain metastasis were associated with more favorable survival. Background: Brain metastases are associated with a poor prognosis in patients with renal cell carcinoma (RCC). The role of targeted therapy in this setting is not well established. The primary objective was to assess overall survival (OS) and neurologic events in patients with brain metastasis treated with targeted agents. Patients and Methods: Patients with RCC treated with targeted agents for brain metastasis between 2002 and 2012 were retrospectively identified. Kaplan-Meier methodology and a Cox proportional hazards model were used to analyze the association between clinical features and OS. Results: Of 65 patients identified, 52 (80%) were treated with antiangiogenic agents and 13 (20%) received inhibitors of mTOR (mechanistic target of rapamycin [serine/threonine kinase]); 57 (88%) had local therapy for brain metastasis, including surgery in 3 (5%), radiation therapy in 36 (55%), and both surgery and radiotherapy in 18 (28%). Median follow-up was 12.3 months (1.1-58.8). Median treatment duration for targeted therapy as first-line therapy was 3.4 months (0.3-31.9). The median OS was 12.2 months (95% CI, 8.0-15.5). The risk group according to the Memorial Sloan Kettering Cancer Center (MSKCC) stratification (P = .001), the histology subtype (clear vs. other) (P < .0001), and the number of brain lesions (1 vs. >= 2) (P = .004) correlated with OS on multivariate analysis. Neurologic complications were identified in 5 patients (8%), including 2 with radiation necrosis and 3 with brain metastasis hemorrhage. Conclusion: The use of targeted agents in the multimodal treatment of patients with RCC and brain metastasis was not associated with excessive neurologic adverse events. Clear cell histology, favorable MSKCC risk status, and solitary brain metastasis are associated with more favorable OS.