Assessing EGFR-mutated NSCLC with bone metastasis: Clinical features and optimal treatment strategy

Cancer Med. 2024 Apr;13(7):e7152. doi: 10.1002/cam4.7152.

Abstract

Background: This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR-tyrosine kinase inhibitors (TKIs).

Methods: The study included patients with stage IV EGFR-mutated NSCLC who were receiving first-line treatment with EGFR-TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not.

Results: The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression-free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM.

Conclusions: The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.

Keywords: antiangiogenesis; bone metastasis; chemotherapy; denosumab; epidermal growth factor receptor; tyrosine kinase inhibitor.

MeSH terms

  • Acrylamides*
  • Aniline Compounds*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Denosumab / therapeutic use
  • ErbB Receptors / genetics
  • Humans
  • Indoles*
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines*
  • Retrospective Studies

Substances

  • osimertinib
  • ErbB Receptors
  • Denosumab
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • Acrylamides
  • Aniline Compounds
  • Indoles
  • Pyrimidines