Does Bone-targeted Therapy Benefit Patients with Metastatic Renal Cell Carcinoma?

In metastatic renal cell carcinoma (mRCC), the bone is the second most common site of metastasis and is associated with increased morbidity and poorer quality of life. Bone-targeted therapies (BTTs) such as denosumab and zoledronic acid may prevent skeletal-related events (SREs). However, the benefit of BTTs in combination with tyrosine kinase inhibitors (TKIs) remains unclear.

We performed a retrospective chart review at the Urologic Cancer Centre for Research and Innovation. Patients with mRCC were included if they had bone metastases treated with TKIs between 2010 and 2017. Our primary outcome was overall survival (OS), defined as the time elapsed from clinical diagnosis of mRCC to death, and modelled using the Kaplan-Meier method. Secondary outcomes included the median time to SRE and the analysis of prognostic factors of OS using Cox proportional hazards regression.

In total, 230 patients with mRCC were identified; of which, 46 had bone metastases treated with TKIs and were included in the study (TKI-only, n = 37; TKI + BTT, n = 9). In the TKI + BTT cohort, patients received either denosumab (n = 5) or zoledronic acid (n = 4). At the time of analysis, 63% of patients were deceased. We observed an OS trend favouring the TKI + BTT cohort (13.8 months [95% confidence interval {CI}: 12.3-15.2] vs. 29.6 months [95% CI: 7.2-51.9], hazard ratio [HR]: 1.66 (95% CI: 0.62-4.45), P = 0.31). When patients in the TKI + BTT cohort were stratified by type of therapy (denosumab or zoledronic acid), the median time to SRE was similar between the groups (4.2 months [95% CI: 2.28-6.14] vs. 2.2 months [95% CI: not available], P = 0.71]. On univariate or multivariate analysis, it was found that age, gender, comorbidities, International metastatic RCC database consortium (IMDC) prognostic group and pathologic tumour grade were not significant predictors of worse OS. Pathologic stage 3 or 4 was an independent predictor of worse OS (HR: 5.8, 95% CI: 1.41-24.03, P = 0.015).

BTTs may have a continued role in the era of targeted therapy and immunotherapy. Further prospective data are required to validate our findings.