DENOSUMAB VERSUS ZOLEDRONIC ACID IN PATIENTS WITH METASTATIC BONE DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS BASED ON RANDOMIZED CONTROLLED TRIALS

Metastatic bone disease (MBD) presents significant challenges in patient management, often leading to skeletal-related events (SREs), compromised quality of life (QOL), and heightened pain experiences. Denosumab (Dmab) and zoledronic acid (ZA) are two bone modifying agents commonly employed to mitigate the sequelae of MBD, yet their comparative efficacy across multiple outcomes in various primary cancer types has yet to be reported in a single analysis. In comparing Dmab with ZA in patients suffering from MBD, we aim to contribute to future work in generating comprehensive evidence-based standardized treatment protocols. A literature search was performed using MEDLINE and EMBASE. Primary outcomes included SRE incidence, overall survival, time to first on-study SRE, pathologic fracture, and radiation to bone. Secondary outcomes included adverse events (AEs), pain, QOL, analgesia usage, and cost-effectiveness. A meta-analysis was performed using random and fixed-effects models to pool effect sizes across studies. Literature search returned seven randomized controlled trials meeting inclusion criteria for meta-analysis and nine studies for cost-assessment. Dmab was superior to ZA in reducing radiation to bone and delaying time to SREs. There were no differences in overall survival, disease progression, or pathological fracture. Dmab is safe for use in MBD and demonstrated superiority to ZA resulting in fewer AEs in the overall MBD population. However, within the prostate cancer subgroup, Dmab was inferior to ZA resulting in greater total AEs and hypocalcemia. Dmab also demonstrated superiority over ZA in delaying time to worsening pain and time to increased pain interference in patients with no/mild pain at baseline. In all cost studies except for two, Dmab had higher mean costs than ZA, and cost per quality-adjusted life years gained was variable ranging from $21,365.03 to $5,643,804.04 The results of our meta-analysis and systematic review demonstrate that Dmab is safe and effective in reducing SREs, AEs, and time to worsening pain, though consensus regarding cost-effectiveness remains variable due to differing drug costs internationally. This research also underscores the therapeutic advantages of Dmab in pain management and QOL, with fewer patients progressing to high opioid usage, although sufficient evidence across studies is lacking. Our findings underscore the importance of tailoring treatment strategies to primary cancer type and individual patient profiles, with the goal of enhancing providers’ understanding of the utility of these agents in the MBD patient population.