Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: A New Definition

Strategic Insights -

A significant challenge in the treatment of non-small cell lung cancer (NSCLC) arises when patients develop resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). According to recent research from the United States, approximately 70% of patients with NSCLC and EGFR mutations experience significant tumor regressions when treated with EGFR TKIs such as gefitinib or erlotinib. However, the majority of these patients inevitably acquire resistance to these drugs. A team of scientists from Vanderbilt University, led by D. Jackman, has proposed a new definition for acquired resistance to EGFR TKIs in NSCLC.

Key Takeaways:

  • Approximately 10% of North American patients with NSCLC have tumors with somatic mutations in the EGFR gene.
  • 70% of patients with EGFR mutations in NSCLC experience significant tumor regressions when treated with EGFR TKIs gefitinib or erlotinib.
  • The new definition of acquired resistance to EGFR TKIs requires patients to have received previous treatment with a single-agent EGFR TKI, and either has a tumor with an EGFR mutation associated with drug sensitivity or has experienced objective clinical benefit from treatment.
  • The definition also requires systemic progression of disease while on continuous treatment with gefitinib or erlotinib within the last 30 days, and no intervening systemic therapy between cessation of gefitinib or erlotinib and initiation of new therapy.
  • The proposed definition aims to minimize reporting of false-positive and false-negative activity in clinical trials and facilitate the identification of agents that truly overcome acquired resistance to gefitinib and erlotinib.

Statistics:

  • 10% of North American patients with NSCLC have tumors with somatic EGFR mutations.
  • 70% of patients with EGFR mutations experience significant tumor regressions when treated with EGFR TKIs gefitinib or erlotinib.
  • 30 days is the timeframe within which systemic progression of disease is considered while on continuous treatment with gefitinib or erlotinib.

Sources:

  • D. Jackman et al., "Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer." Journal of Clinical Oncology, 2010; 28(2): 357-60.