# Impact of bone-targeting agents on the clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab: a sub-analysis of the Meet-URO 15 study

## TL;DR

This study found that bone-targeting agents, especially denosumab, improved survival and delayed disease progression in kidney cancer patients with bone metastases treated with nivolumab.

## Contribution

The study is the first to show that specific bone-targeting agents, particularly denosumab, enhance the effectiveness of nivolumab in metastatic renal cell carcinoma patients with bone metastases.

## Key findings

- Bone-targeting agents significantly improved progression-free and overall survival in mRCC patients with bone metastases.
- Denosumab outperformed zoledronic acid and non-BTA treatment in both progression-free and overall survival.
- The survival benefits of bone-targeting agents were confirmed after adjusting for confounding variables.

## Abstract

Immune checkpoint inhibitors have revolutionized the treatment landscape for metastatic renal cell carcinoma (mRCC). However, some patients fail to experience durable benefits, especially those with bone metastases.

This study aimed to evaluate the impact of bone-targeting agents (BTAs), specifically denosumab and zoledronic acid (ZA), on the clinical outcomes of patients with mRCC treated with nivolumab.

This retrospective study analyzed data from the Meet-URO 15 trial on patients with mRCC who received nivolumab, categorizing them into BTA and non-BTA groups. Survival outcomes were assessed, with inverse probability of treatment weighting (IPTW) adjustment for confounding variables. Subsequently, the specific impact of different BTAs on the clinical outcomes was explored.

Of 203 mRCC patients with bone metastases, 38 received BTAs (BTA group) while 138 did not (non-BTA group). BTA treatment significantly improved the median progression-free survival (PFS) (291 vs. 117 days, p = 0.005) and overall survival (OS) (960 vs. 397 days, p = 0.008) compared with the non-BTA group, with a reduced risk of death (HR = 0.57, 95%CI = 0.34–0.95, p = 0.031) and progression or death (HR = 0.57, 95%CI = 0.35–0.92, p = 0.023) at multivariate analyses. IPTW adjustment confirmed these survival benefits, with a reduced risk of death (HR = 0.55–95%CI = 0.39–0.76, p < 0.001) and progression or death (HR = 0.58, 95%CI = 0.42–0.79, p < 0.001) in BTA patients. Furthermore, denosumab, compared with ZA and the non-BTA group, demonstrated superior OS (1,662 vs. 681 vs. 411 days, p < 0.001) and PFS (1,101 vs. 242 vs. 132 days, p < 0.001) in the same IPTW-adjusted population.

This study suggests a potential beneficial impact of BTAs, especially denosumab, on the clinical outcomes after nivolumab therapy in mRCC patients with bone metastases. Prospective trials are needed to better define the impact of BTAs in these patients.