Final overall survival results from a phase III, randomized, placebo-controlled, parallel-group study of gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804)

J Thorac Oncol. 2015 Apr;10(4):655-64. doi: 10.1097/JTO.0000000000000445.

Abstract

Background: The results of the Iressa in NSCLC for maintenance study (NCT00770588; C-TONG 0804), which compared gefitinib and placebo as maintenance therapy in patients with advanced non-small-cell lung cancer without disease progression after first-line chemotherapy, were published previously. The objective of this report is to provide a mature analysis of overall survival (OS) for Iressa in NSCLC for maintenance study in intention to treat (ITT) population and in subgroups according to epidermal growth factor receptor (EGFR) mutation status.

Patients and methods: A total of 296 patients were randomly assigned. EGFR mutations were detected using an amplification mutation refractory system. Seventy-nine patients were assessable for EGFR mutations. OS was analyzed by a Cox proportional hazards model adjusted for the same covariates in ITT population and subgroups according to EGFR mutation status.

Results: OS was similar for gefitinib and placebo arm with no significant difference between treatments in ITT population (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.68-1.14; p = 0.335) and in subgroups with wild type EGFR (HR, 1.27; 95% CI, 0.7-2.3; p = 0.431) or unknown EGFR mutations (HR, 0.92; 95% CI, 0.68, 1.25; p = 0.603). In the EGFR mutation-positive subgroup, the gefitinib arm showed a higher OS than the placebo arm (HR, 0.39; 95% CI, 0.15, 0.97; p = 0.036).

Conclusion: EGFR mutation was the strongest predictive biomarker for OS benefit of gefitinib as maintenance treatment. The analyses of OS showed that patients achieve a clear and significant survival benefit if they receive EGFR tyrosine kinase inhibitors as maintenance treatment in EGFR mutation-positive patients.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • China / epidemiology
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Survival Rate / trends
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib

Associated data

  • ClinicalTrials.gov/NCT00770588