Survival Outcomes in EGFR Mutation-Positive Lung Cancer Patients Treated with Gefitinib until or beyond Progression

Oncol Res Treat. 2016;39(10):605-614. doi: 10.1159/000449024. Epub 2016 Sep 15.

Abstract

Background: Discontinuation of gefitinib treatment is often accompanied by a disease flare. Some studies have demonstrated a benefit of the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) beyond progression; however, long-term results of these investigations remain limited.

Patients and methods: We observed 70 patients with EGFR-mutated (EGFR-M+) non-small cell lung cancer (NSCLC) receiving single-agent gefitinib in a routine clinical setting; 56 patients were experiencing RECIST progression at the time of the analysis.

Results: There was a significant increase (p = 0.00001) in overall survival (OS) in patients continuing on gefitinib beyond progression (n = 21; median duration of continued gefitinib use: 4.2 months; median OS: not reached; expected OS: 29.7 months) as compared to those who stopped gefitinib treatment upon disease progression (n = 35; median OS: 14.0 months). The association between extended gefitinib use and improved OS remained true in multivariate Cox regression analysis (hazard ratio = 4.49, 95% confidence interval 1.25-16.09; p = 0.021). Patient selection bias constitutes an essential limitation of this clinical observational study, given that patients with a more favorable disease course and/or high initial tumor sensitivity to TKI treatment were more likely to be considered for prolonged gefitinib use.

Conclusion: This study confirms that continued administration of gefitinib beyond progression is a viable treatment option for some patients with EGFR-M+ NSCLC, in particular those who cannot be rescued by novel EGFR mutation-specific inhibitors such as osimertinib.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Disease Progression
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / prevention & control
  • Prevalence
  • Quinazolines / administration & dosage*
  • Risk Factors
  • Russia / epidemiology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Quinazolines
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib