Potential synergistic effects of bisphosphonates with sorafenib on renal cell carcinoma with bone metastases.

Abstract

496 Background: We evaluated the role of bisphosphonates in conjunction with sorafenib in improving progression-free survival (PFS) and overall survival (OS) in bone metastatic renal cell carcinoma (mRCC) patients. Methods: A total of 81 sorafenib-treated patients were retrospectively divided into 3 groups at our single study center: Group 1 (n=26, sorafenib single agent); Group 2 (n=26, sorafenib plus oral Bonefos); Group 3 (n=29, sorafenib plus intravenous zoledronic acid). Alkaline phosphatase (ALP) before and 12 weeks after treatment were evaluated as prognostic factor for PFS and OS. Results: The majority of the patients were males (67.9%) with mean age of 57.2 ± 11.2 years. Baseline demographic characteristics were similar across the 3 study groups, and the known prognostic factors were balanced across the cohort. There was no significant difference observed in the objective response between the 3 study groups (Group 1 vs. 2 vs. 3; p=0.659); partial remission (8% vs. 8% vs. 10%), stable disease (65% vs. 80% vs. 66%), progressive disease (27% vs. 12% vs. 24%). Median PFS was significantly higher in Group 2 vs 1 vs 2 (18.7 vs. 6.7 vs. 10.5 months; p=0.024). Median OS was 16.8, 22.1, and 20.7 months; p=0.052 in Group 1, 2 and 3, respectively. Multivariate analysis demonstrated that bisphosphonate use (hazard ratio [HR]=0.36, p=0.006), Memorial Sloan Kettering Cancer Center (MSKCC) score (HR=4.10, p<0.001), non-clear cell subtype (HR=1.26, p=0.039), and elevated ALP after 12 weeks’ treatment (HR=3.53, p<0.001) were associated with PFS. MSKCC score (HR=5.24, p<0.001), elevated ALP after 12 weeks’ treatment (HR=4.71, p<0.001), and metastatic organs (HR=1.93, p=0.008) were associated with OS. Bisphosphonates use was not an independent predictor of OS (HR=0.55, p=0.160). Conclusions: Bisphosphonates administered with sorafenib could synergistically improve PFS and OS in RCC with bone metastases, with the benefit of being more efficacious and safer than intravenous zoledronic acid. Elevated ALP following the treatment could be an independent predictor for both PFS and OS in bone mRCC.