(P 118) IMPACT OF TYROSINE KINASE INHIBITOR THERAPY ON BONE PROGRESSION IN PATIENTS WITH DRIVER-MUTATED METASTATIC NON-SMALL CELL LUNG CANCER WITH DE NOVO BONE METASTASES

Objective: In non-small cell lung cancer (NSCLC), 45-60% of patients will develop bone metastases, leading to impaired mobility, increased pain, and reduced quality of life. Although tyrosine kinase inhibitors (TKI) are the standard first-line treatment for patients with metastatic NSCLC (mNSCLC) with EGFR, ALK, ROS, or RET driver mutations, their efficacy in preventing bone metastasis progression (BM-P) and skeletal-related events (SREs) remains unclear.
This study assessed bone metastases progression-free-survival (BM-PFS) and the incidence of SREs in patients with driver-mutated mNSCLC with de novo bone metastases treated with first-line TKI.

Methods: We conducted a single-institution retrospective analysis of patients with driver-mutated mNSCLC treated with first-line TKI monotherapy between 01/2017-12/2024. We assessed BM-PFS and incidence of SREs, including pathological fractures requiring orthopedic surgery and/or radiotherapy, pain, spinal cord compression, and hypercalcemia.

Results: 105 patients were included with median follow-up of 34.2 months (Table 1). Progression occurred in 69 (65.7%) patients with PFS of 25.7 months (Figure 1). Twenty-two (21%) patients experienced BM-P, including oligoprogression. BM-PFS was 63.6 months; however, of the patients who experienced BM-P, median time-to-event was 9.4 months. Fifteen patients (14.2%) experienced >1 SRE, with a median time-to-event of 8.3 months. SRE was predictive of BM-P (HR 5.28, p=0.006). Three-year overall survival (OS) was 77%. BM-P was not predictive for OS.

Conclusion: TKIs appear to be protective against BM-P, but there remains a small subset of patients who experience BM-P early in their disease course, often preceded by SRE. Encouragingly, BM-P was not associated with decreased OS, as prior studies indicated. Understanding BM-P and SREs in response to targeted therapy is critical in guiding treatment to reduce the morbidity and mortality of mNSCLC.