Denosumab combined with immunotherapy, radiotherapy, and granulocyte-macrophage colony-stimulating factor for the treatment of metastatic nasopharyngeal carcinoma: A case report

Bone is a major site of metastasis in nasopharyngeal carcinoma (NPC). Recently, nuclear factor kappa-beta ligand (RANKL) inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption, as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1 (PD-1) inhibitor therapy. We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy. Prior to chemotherapy, the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions. However, the patient received combination therapy, including RANKL inhibitors (denosumab) alongside PD-1, radiotherapy, and granulocyte-macrophage colony-stimulating factor (PRaG) therapy (NCT05435768), and achieved 16 months of progression-free survival and more than 35 months of overall survival, without encountering any grade 2 or higher treatment-related adverse events. Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.