Risk factors of skeletal-related events in patients with bone metastasis from non-small cell lung cancer undergoing treatment with zoledronate-a post hoc analysis of a randomized clinical trial

Background Skeletal-related events (SREs) are critical events for patients with bone metastasis from non-small cell lung cancer (NSCLC). Thus, bone-modifying agents are recommended in this population. However, the baseline risk factors of SREs in patients with bone metastasis from NSCLC are not well established. Methods We analyzed the patient-level data from the zoledronate arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastasis (ClinicalTrial.gov ID: NCT00330759) available at Project Data Sphere, a broad-access research platform. The primary endpoint was the first SRE from the inclusion to the trial, and the time to the first SRE was analyzed using Cox proportional hazards model. Results We analyzed 302 patients with NSCLC without a documented history of osteopenia or osteoporosis included in the zoledronate arm of the trial. Ninety-eight patients (32%) had at least one SRE. The univariate analysis showed that low serum albumin and elevated serum alkaline phosphatase (ALP) are significant baseline risk factors for SREs (hazard ratio (HR) [95% confidence interval (CI)]; 2.27 [1.43-3.61], and 1.91 [1.26-2.90], respectively). Additionally, osteoblastic and mixed type of bone metastasis showed a significantly lower risk of SREs compared with the osteolytic lesion (HR [95% CI]; 0.39 [0.21-0.72], and 0.31 [0.15-0.63], respectively). These factors also showed a significant association with the risk of SREs in multivariate analysis. Conclusions We revealed that osteolytic bone metastasis, low serum albumin, and elevated serum ALP are risk factors for SREs in patients with bone metastasis from NSCLC.