Impact of bone and liver metastases (BM, LM) in patients with metastatic renal cell carcinoma (mRCC) treated with molecularly targeted agents (MTAs): Results from the International mRCC Database Consortium (IMDC).

394 Background: The skeleton and liver are frequently involved sites of metastases in patients with mRCC. Their impact on survival outcomes of patients treated with currently approved MTAs is largely unknown. The purpose of this study was to analyze patient outcomes based on the presence or absence of BM and/or LM in the era of MTAs. Methods: We conducted a review from the IMCD of 2,027 patients with mRCC treated from April 2003 to August 2012. Statistical analyses were performed using Cox regression and the Kaplan-Meier method. Results: Median follow-up was 21 months. 1,978 were treated with first-line VEGF targeted therapy and 49 were treated with first-line mTOR inhibitors. Presence of BM was 34% overall and 27%, 33%, and 43% in favorable, intermediate, and poor-risk disease, respectively, by IMDC criteria (p < 0.001). Presence of LM was 19% overall and higher in poor-risk patients (23%) compared to favorable (20%) or intermediate-risk groups (16%) (p = 0.003). Other sites of metastases include lung, lymph node, adrenal, soft tissue, and/or brain. Among patients with a single metastatic site, those with BM or LM had a worse overall survival (OS) when compared to metastases at other sites (Table). Among patients with ≥ 2 sites of metastases, those with BM and LM had a shorter time to treatment failure (4.2 vs. 7.3 months, p < 0.0001) and worse OS (Table) when compared to patients with metastases at other sites. In multivariable analyses adjusting for IMDC criteria, BM and LM independently predicted poorer survival (HR=1.38 for BM vs. other metastases, 1.37 for LM vs. other metastases, and 1.82 for concomitant BM and LM, respectively, p < 0.0001). Conclusions: BM and LM in mRCC patients have significant clinical relevance and may possibly be used for risk-stratification of patients with mRCC. [Table: see text]