Dissociated skeletal response to first-line immunotherapy in synchronous bone metastatic non-small cell lung cancer patients: Clinical profiles and survival benefit of denosumab adjunction

Introduction: Patients with bone metastases (BM) from non-small cell lung cancer (NSCLC) derive less clinical benefit from immune checkpoint inhibitors (ICIs) than those without skeletal involvement. We aimed to characterize bone-specific disease control profiles under first-line ICI therapy and explore the association of denosumab with clinical outcomes. Methods: We conducted a multicenter retrospective study in BM-NSCLC patients, naïve to systemic therapy, treated with first-line ICI monotherapy, with or without denosumab. Radiological response in soft tissue and bone compartments was assessed at 6 months using iRECIST. Disease control (DCR: iCR, iPR, or iSD) and dissociated response (discordant DCR between compartments) were predefined. Denosumab impact was evaluated using logistic regression and Cox models. Conclusion: mutation, and systemic inflammation are potential determinants of bone-specific resistance. While denosumab did not significantly modify bone DCR, its trend toward association with improved progression-free survival and reduced risk of progression or death generates the hypothesis of an immunomodulatory effect warranting prospective evaluation.