Clinical implications of isolated bone failure without systemic disease progression during EGFR-TKI treatment

• Published in: Clinical lung cancer Vol. 17; no. 6; pp. 573 - 580.e1
• Main Authors: Hwang, Ji An, MD, Lee, Ji Young, MD, Kim, Woo Sung, MD, PhD, Song, Joon Seon, MD, Rho, Jin Kyung, PhD, Choi, Chang-Min, MD, PhD, Lee, Jae Cheol, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Bone Diseases - chemically induced; Bone Diseases - pathology; Bone metastasis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Disease Progression; Epidermal growth factor receptor; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Mutation - genetics; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Non–small-cell lung cancer; Prognosis; Protein Kinase Inhibitors - adverse effects; Pulmonary/Respiratory; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Retrospective Studies; Skeletal-related event; Survival Rate; Tyrosine kinase inhibitor; non-small cell lung cancer; tyrosine kinase inhibitor; disease progression; bone metastasis; skeletal-related event; epidermal growth factor receptor; Non–small-cell lung cancer; Bone metastasis; Tyrosine kinase inhibitor; Epidermal growth factor receptor; Skeletal-related event
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2016.05.018

Abstract Background We aimed to investigate the characteristics of EGFR-mutant non-small cell lung cancer (NSCLC) patients who experienced isolated progression of bone metastases without aggravation of extra-skeletal organs during EGFR-TKI treatment. Methods We retrospectively reviewed 870 EGFR-mutant NSCLC patients treated with EGFR-TKI between 2004 and 2014. Among them, patients who received radiation therapy to bone metastases due to the occurrence of skeletal-related events (SREs), impending SREs, or medically uncontrolled bone pain were selected and defined as ‘bone failure (BF)’. BFs were classified into two categories according to the presence of accompanying disease progression in extra-skeletal organs: isolated bone failure (IBF) and non-IBF. Results Among the 71(8.2%) BF patients, 33(46.5%) experienced IBF without aggravation of disease in extra-skeletal organs. IBF was more frequent in clinical benefit group (responders and stable≥6 months) than in non-clinical benefit group (54.4% vs.14.3%; P =0.007), along with good performance status([PS], 82.5% vs.42.9%; P =0.005) and 19 deletion(68.4% vs.35.7%; P =0.024). Female sex, good PS, 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 =0.034,ECOG 0 or 1:87.9% vs.63.2%; P =0.017,clinical benefit from TKI:93.9% vs.68.4%; P =0.007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted OR,6.647;95% CI,1.328–33.262; P =0.021). Patients with IBF tended to exhibit longer survival times from the initiation of TKI (20.7 vs.11.1 months; P =0.2) and from BF (8.6 vs.3.4 months; P =0.186). Conclusions IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival necessitating following studies to explore the differential activity of EGFR-TKI in bones over time or over other organs.