Femoral bone metastasis is a poor prognostic factor in osimertinib-treated patients with EGFR-mutated non-small cell lung cancer

Abstract Objectives: Epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC) have higher frequency of bone metastases than those of wild type; however, the metastatic pattern and the influence on clinical outcome remains unclear. Therefore, we retrospectively analyzed the association between bone metastatic sites and the clinical efficacy of the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib, in these patients. Methods: Clinical data of patients with advanced-NSCLC harboring EGFR mutation (N=411) at five medical institutions were retrospectively assessed for bone metastatic sites, overall survival (OS) and progression-free survival (PFS). Results: Bone metastases was found in 41.1% of the patients at diagnosis, including 13.1% for single lesion, 8.0% for double lesions, and 20.0% for multiple lesions (≥3). Among them, vertebra (76.3%) and pelvis (60.9%) were most frequent metastatic sites. Femoral-, sternum-, and scapula-metastases were remarkably increased in the patients with multiple-bone metastasis. In the common EGFR -mutant NSCLC patient treated with osimertinib, both the OS and the PFS of the patients with femoral bone metastasis were remarkable significant shorter than those of the patients without femoral bone metastasis (OS; not reached vs. 12.1 months, P < 0.0001, and PFS; 17.2 vs. 9.3 months, P < 0.0018). Furthermore, a multivariable cox regression analysis, including several poor prognostic factors such as L858R mutation and liver metastasis, demonstrated that femoral bone metastasis was a statistically independent predictor of OS. Conclusion: Femoral bone metastasis is notably associate with poor survival of EGFR -mutant NSCLC patients who were treated with osimertinib, and is an independent prognostic factor of OS.