Clinical Characteristics and Continued Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Administration in EGFR-mutated Non-Small Cell Lung Cancer with Skeletal Metastasis

Cancer Res Treat. 2016 Jul;48(3):1110-9. doi: 10.4143/crt.2015.289. Epub 2016 Jan 6.

Abstract

Purpose: The aim of this study was to analyze clinical characteristics of skeletal metastasis in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) and treatment outcomes of continued EGFR tyrosine kinase inhibitor (TKI) therapy in patients presenting with skeletal metastasis progression.

Materials and methods: Of the 216 patients treated with EGFR-TKI for management of stage III-IV NSCLC between 2006 and 2012 in Seoul St. Mary's Hospital, 76 patients with confirmed EGFR-mutated NSCLC with skeletal metastases during therapy were analyzed retrospectively.

Results: Of 76 patients with EGFR mutant lung cancer with skeletal metastasis, 37 patients developed first progressive disease (PD) in skeletal regions. EGFR-TKI was continued in these 37 patients after first PD in skeletal regions. Median time to first PD of skeletal regions was 8.9 months (95% confidence interval [CI], 4.8 to 13.0). Median time of continued EGFR-TKI after first PD of skeletal regions was 8.0 months (95% CI, 2.9 to 13.0) in patients with disease progression of preexisting regions, 5.6 months (95% CI, 4.5 to 6.7) in patients showing new localized regions, and 3.3 months (95% CI, 1.1 to 5.5) in patients with multiple new metastatic regions (p=0.006). Median time of postskeletal metastasis progression survival was 23.0 months (95% CI, 13.5 to 32.5), 15.0 months (95% CI, 3 to 34.7), and 7.0 months (95% CI, 6.0 to 8.0) (p=0.004) in the above described patient groups, respectively. Overall, seven patients (18.9%) had more than one episode of skeletal progression of disease without extraskeletal PD.

Conclusion: Continued EGFR-TKI treatment with adequate local treatment after progression of skeletal metastasis may be considered for patients who show disease progression in preexisting regions or local progression.

Keywords: Bone metastasis; EGFR; EGFR tyrosine kinase inhibitor; Non-small cell lung carcinoma; Response Evaluation Criteria in Solid Tumors.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Positron Emission Tomography Computed Tomography
  • Protein Kinase Inhibitors / therapeutic use*
  • Response Evaluation Criteria in Solid Tumors
  • Retrospective Studies
  • Seoul
  • Time Factors
  • Treatment Outcome

Substances

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