Different treatment orders achieved similar clinical results: a retrospective study for retreatment of epidermal growth factor receptor tyrosine kinase inhibitors in 120 patients with non-small-cell lung cancer

J Cancer Res Clin Oncol. 2014 Mar;140(3):427-33. doi: 10.1007/s00432-014-1582-x. Epub 2014 Jan 9.

Abstract

Background: It was reported the retreatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may bring benefit to non-small-cell lung cancer (NSCLC) patients who benefited previously. Nevertheless, the treatment order in most of the prior literature was gefitinib (G) to erlotinib (E), and little was known about whether other treatment order may also bring benefit to the patients.

Methods: One hundred and twenty NSCLC patients who received EGFR-TKIs treatment twice were enrolled in this study. The safety and effectiveness of the second EGFR-TKIs administration, as well as the influencing factors that contribute to this process, were analyzed retrospectively.

Results: Forty-nine (40.8%) patients were retreated with same kind of EGFR-TKIs: 30 (25%) were G and 19 (15.8%) were E. Seventy-one (59.2%) patients switched to another kind: 55 (45.8%) were G to E and 16 (13.4%) were the reverse. Notably, no differences in clinical benefits were found among the four different treatment orders. For the second administration, the adverse effects of all patients were generally classified as grade I-II and the 1-year survival rate reached 32.5%. The objective response rate, disease control rate, median progression-free survival (PFS), and overall survival was 10.0% (12/120), 52.5% (63/120), 2.3 (95% CI 1.5-3.0) months and 8.0 (95% CI 7.0-8.5) months, respectively. The univariate and multivariate analyses revealed that those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration, and the strongest beneficial indicators of the retreatment were PFS of the initial EGFR-TKIs (≥6 months, HR 0.611, 95% CI 0.354-0.901, P = 0.0076) and time interval between the two EGFR-TKIs treatment (≥4 months, HR 0.529, 95% CI 0.328-0.852, P = 0.0088).

Conclusion: Those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration. A time interval of ≥4 months may improve the retreatment, but differences in clinical benefit were not found among different treatment orders. If the retrospective result could be validated further in the future, it would be helpful for rational administration of EGFR-TKIs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Retreatment
  • Retrospective Studies
  • Smoking / adverse effects
  • Smoking / epidemiology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib