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

Clin Lung Cancer. 2016 Nov;17(6):573-580.e1. doi: 10.1016/j.cllc.2016.05.018. Epub 2016 Jun 11.

Abstract

Background: 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.

Results: 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).

Conclusion: 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.

Keywords: Bone metastasis; Epidermal growth factor receptor; Non–small-cell lung cancer; Skeletal-related event; Tyrosine kinase inhibitor.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Diseases / chemically induced
  • Bone Diseases / pathology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Protein Kinase Inhibitors / adverse effects*
  • Retrospective Studies
  • Survival Rate

Substances

  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors