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Published on: August 11, 2017
Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer
Humberto Lara-Guerra1, Thomas K Waddell, Maria A Salvarrey
1University Ave, Toronto, Ontario, Canada M5G 2M9.
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 alpha 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.
Insights
Preoperative gefitinib is safe for early non-small-cell lung cancer (NSCLC). EGFR mutation predicted response, suggesting potential for personalized treatment in early NSCLC.
Area of Science:
- Oncology
- Thoracic Surgery
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in advanced non-small-cell lung cancer (NSCLC).
- The role of EGFR TKIs in early-stage NSCLC remains unestablished.
- Preoperative (neoadjuvant) therapy can potentially improve outcomes in early-stage cancers.
Purpose of the Study:
- To evaluate the safety and efficacy of preoperative gefitinib in clinical stage I NSCLC.
- To assess tumor response to gefitinib in the neoadjuvant setting.
- To identify clinical and molecular predictors of treatment response in early NSCLC.
Main Methods:
- An open-label, single-arm study involving patients with clinical stage I NSCLC.
- Patients received gefitinib 250 mg/day for up to 28 days before surgery.
- Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST).
- Molecular analyses included EGFR and KRAS mutation status, EGFR protein expression, and gene copy number.
Main Results:
- Thirty-six patients completed preoperative gefitinib treatment.
- Grade 3 toxicities were infrequent (rash, diarrhea, elevated ALT).
- Tumor shrinkage was observed in 11% (partial response) and disease progression in 9%.
- EGFR mutations were identified as the strongest predictor of treatment response.
- Tumor EGFR protein expression was noted in 83% of patients.
Conclusions:
- Preoperative gefitinib is a safe and feasible neoadjuvant regimen for early-stage NSCLC.
- This approach provides a valuable trial design for identifying predictors of treatment response.
- Findings support further investigation into targeted therapies for early NSCLC based on molecular profiles.
