Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib

Lung Cancer. 2017 Jun:108:109-114. doi: 10.1016/j.lungcan.2017.03.010. Epub 2017 Mar 24.

Abstract

Objectives: Patients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients.

Materials and methods: We reviewed 189 patients treated with erlotinib for mEGFRmt NSCLC. We classified first pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF), and used competing-risks regression to identify factors associated with ISF, progression and overall survival (OS). We also separately analyzed intracranial and intrathoracic failure.

Results: Of 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age and lack of initial CNS involvement independently correlated with ISF, with a trend for higher T and N stage. Higher T and N stage was also a significant predictor of progression. Factors predicting shorter OS were female gender, weight loss, initial intracranial involvement, and ≥4 extracranial metastases. Intrathoracic progression was a component of first failure in 61%, and three-year cumulative incidence of brain metastasis was 30%.

Conclusion: The main pattern of progression in mEGFRmt NSCLC on erlotinib is in the initial sites of disease. Younger patients and those without brain involvement are particularly likely to develop ISF. This suggests a role for incorporating local therapy into treatment of selected patients with mEGFRmt NSCLC.

Keywords: CNS; EGFR; Erlotinib; NSCLC; Oligometastatic.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Disease Progression
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / adverse effects
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Positron-Emission Tomography
  • Prognosis
  • Survival Analysis
  • Treatment Failure
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Erlotinib Hydrochloride
  • ErbB Receptors