Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer

Humberto Lara-Guerra, Thomas K. Waddell, Maria A. Salvarrey, Anthony M. Joshua, Catherine T. Chung, Narinder Paul, Scott Boerner, Akira Sakurada, Olga Ludkovski, Clement Ma, Jeremy Squire, Geoffrey Liu, Frances A. Shepherd, Ming Sound Tsao, Natasha B. Leighl

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response. Patients and Methods: Patients received gefitinib 250 mg/d for up to 28 days, followed by mediastinoscopy and surgical resection in an open-label, single-arm study. Tumor response was evaluated by Response Evaluation Criteria in Solid Tumors. Blood samples and tumor biopsies were collected and analyzed for transforming growth factor α level, EGFR protein expression, EGFR gene copy number, and EGFR (exon 19 to 21) and KRAS mutations. Results: Thirty-six patients completed preoperative treatment (median duration, 28 days; range, 27 to 30 days). Median follow-up time is 2.1 years (range, 0.86 to 3.46 years). Three patients experienced grade 3 toxicities (rash, diarrhea, and elevated ALT). Tumors demonstrated EGFR-positive protein expression in 83%, high gene copy number in 59%, EGFR mutations in 17%, and KRAS mutations in 17%. Tumor shrinkage was more frequent among women and nonsmokers. Partial response was seen in four patients (11%), and disease progression was seen in three patients (9%). The strongest predictor of response was EGFR mutation. Conclusion: Preoperative window therapy with gefitinib is a safe and feasible regimen in early NSCLC and provides a trial design that may better inform predictors of treatment response or sensitivity.

Original languageEnglish
Pages (from-to)6229-6236
Number of pages8
JournalJournal of Clinical Oncology
Issue number36
Publication statusPublished - 2009 Dec 20
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer'. Together they form a unique fingerprint.

Cite this