Clinical Implications of Isolated Bone Failure Without Systemic Disease Progression During EGFR-TKI Treatment

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We investigated the characteristics of patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) who had experienced isolated progression of bone metastases without aggravation of extraskeletal organs during EGFR-tyrosine kinase inhibitor (TKI) treatment.

Materials and Methods

We retrospectively reviewed the data from 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014. Of these patients, 71 (8.2%), who had undergone radiation therapy to bone metastases because of skeletal-related events, impending skeletal-related events, or medically uncontrolled bone pain, were selected and defined as having bone failure (BF). BFs were classified into 2 categories according to the presence of accompanying disease progression in extraskeletal organs: isolated BF (IBF) and non-IBF.


Of the 71 BF patients, 33 (46.5%) experienced IBF without aggravation of disease in extraskeletal organs. IBF was more frequent in the clinical benefit group (responders and stable for ≥ 6 months) than in nonclinical benefit group (54.4% vs. 14.3%; P = .007). IBF was also more frequent in those with good performance status (82.5% vs. 42.9%; P = .005) and 19 deletion (68.4% vs. 35.7%; P = .024). Female sex, good performance status, and clinical benefit from TKI were more frequent in patients with IBF than in those with non-IBF (female sex, 69.7% vs. 44.7%; P = .034; Eastern Cooperative Oncology Group 0 or 1, 87.9% vs. 63.2%; P = .017; clinical benefit from TKI, 93.9% vs. 68.4%; P = .007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted odds ratio, 6.647; 95% confidence interval, 1.328-33.262; P = .021). Patients with IBF tended to exhibit longer survival times from the initiation of the TKI (20.7 vs. 11.1 months; P = .2) and from the onset of BF (8.6 vs. 3.4 months; P = .186).


IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival. This finding requires future studies to explore the differential activity of EGFR-TKI in the bones over time or in preference to other organs.


Of 870 patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer, 71 (8.2%) received radiation therapy to metastatic bone lesions during EGFR-tyrosine kinase inhibitor (TKI) therapy. Of these patients, isolated progression of bone metastasis without aggravation of other extraskeletal organs occurred more frequently in patients with clinical benefits from EGFR-TKIs (54.4% vs. 14.3%; P = .007), resembling isolated central nervous system failure. The differential activity of EGFR-TKI in the bones over time or in preference to other organs should be explored in future studies.

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