Comparative efficacy and safety of bisphosphonates and other bone-modifying agents in patients with bone metastases from lung cancer: A systematic review and Bayesian network meta-analysis.

Abstract

e20006 Background: Bone metastases from lung cancer are common and significantly affect patient quality of life, leading to pain, skeletal-related events (SREs), and reduced survival. Bone-modifying agents (BMAs), including bisphosphonates and denosumab, are widely used to manage these complications. However, the comparative efficacy and safety of BMAs in this setting remain unclear. This network meta-analysis aims to evaluate the relative effectiveness of BMAs in improving clinical outcomes for lung cancer patients with bone metastases. Methods: A systematic review was conducted to identify clinical studies comparing bisphosphonates, and denosumab in lung cancer patients with bone metastases. A Bayesian network meta-analysis was performed, pooling mean differences (MDs) and risk ratios (RRs) with 95% credible intervals (CrIs) using random or fixed effects models based on deviance information criteria (DIC). Surface Under the Cumulative Ranking Curve (SUCRA) values were used to rank interventions across outcomes, including overall survival (OS), progression-free survival (PFS), osteonecrosis of jaw (ONJ), and skeletal-related events (SREs). Results: A total of 10 studies involving 2,035 patients were included. For OS, Pamidronate ranked highest (MD = 28.27, 95% CrI: 3.15–53.45, SUCRA: 92.49%), followed by Denosumab (MD = 14.24, 95% CrI: -7.58–36.02, SUCRA: 64.62%). Zoledronic Acid showed moderate efficacy (MD = 4.21, 95% CrI: -5.32–13.56, SUCRA: 34.1%) and no treatment ranked lowest (SUCRA: 8.8%). For PFS, no treatment had the highest SUCRA value (89.67%), with Denosumab (MD = -2.76, 95% CrI: -29.80–6.54, SUCRA: 45.07%) and Zoledronic Acid (MD = -4.69, 95% CrI: -24.4–2.54, SUCRA: 15.26%) showing limited efficacy. Conclusions: Pamidronate was identified as the most effective BMA for improving survival, while Denosumab demonstrated a strong effect in reducing skeletal-related events but was associated with a higher risk of adverse events. Zoledronic Acid and Ibandronate showed moderate efficacy with favorable safety profiles. These findings provide evidence-based guidance for selecting optimal BMAs and supporting clinical decision-making in this patient population. Intervention/Outcome(MD/RR, 95% CrI, SUCRA) OS PFS ONJ SREs Denosumab 14..24-7.58–36.02, 64.62 -2.76 -29.80–6.54, 45.07 12.230.47–632.94, 8.8 1.07 0.40–2.90, 66.99 No Treatment(Control, SUCRA) 8.8 89.67 60.56 74.1 Pamidronate 28.27 3.15–53.45, 92.49 NA NA NA Zoledronic Acid 4.21 -5.32–13.56, 34.1 -4.69-24.4–2.54,15.26 0.810.07–7.51,67.24 1.430.62–3.36,40.04 Ibandronate NA NA 0.790.00–101.58,63.41 2.180.51–10.21,18.88