The Association Between Longitudinal Changes in TRACP-5b and Bone Metastasis Progression During Osimertinib Therapy

Background/Aim: Bone metastases (BMs) of non-small cell lung cancer (NSCLC) are associated with skeletal-related events that impair quality of life. Tartrate-resistant acid phosphatase 5b (TRACP-5b) is considered a marker of osteoclastic activity; however, its prognostic utility for NSCLC patients with BMs remains unclear. This study aimed to evaluate the association between longitudinal changes in TRACP-5b and BM progression in a relatively homogeneous population of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC treated with osimertinib. Patients and Methods: Patients with EGFR-mutated NSCLC receiving osimertinib between January 2019 and May 2024 were retrospectively identified. Serum TRACP-5b levels were measured at five predefined time points: osimertinib initiation (Point 1), the first computed tomography scan for response evaluation (Point 2), the two assessments immediately preceding disease progression (Points 3 and 4), and the time of progression (Point 5). Patients were classified by BM progression status and matched 1:1 on prior denosumab administration and EGFR mutation type to reduce baseline imbalance. Mixed-effects models for repeated measures were used to assess longitudinal differences in TRACP-5b levels, adjusting for relevant covariates. Results: Thirty-six patients (18 per group) were included. Least-squares mean TRACP-5b levels were generally comparable between groups from Points 2 to 4, whereas higher levels were observed at Point 5 in the BM progression group (difference, 49.4 mU/dl; 95%CI=3.0-95.7). TRACP-5b levels increased from Points 3 to 5 only in the BM progression group. Conclusion: Serial monitoring of TRACP-5b may provide supplementary information for detecting BM progression in patients with NSCLC treated with osimertinib.