Surgery for Early Lung Cancer With Preoperative Erlotinib (Tarceva): A Clinical Phase II Trial (SELECT)

2.5 Rationale for preoperative erlotinib therapy Erlotinib is the only EFGR tyrosine kinase inhibitor to demonstrate a survival advantage and symptom improvement in a large phase III trial after failure of chemotherapy in advanced non-small cell lung cancer (Shepherd, Rodrigues Pereira et al. 2005). Although the potential utility of erlotinib in earlier stage NSCLC is unclear, given its activity in advanced disease and its minimal toxicity profile, there is likely a subset of patients who may benefit and potentially be cured by adjuvant erlotinib therapy. Erlotinib may also have greater antitumour activity in earlier stage disease. Therefore, we propose a phase II study to assess erlotinib pre-operatively in clinical stage 1 and 2 NSCLC, and downstream effects on signal transduction pathways and possible markers of treatment resistance and sensitivity. The proposed study involves administering oral erlotinib for four weeks (28 days) preoperatively in early stage (1A/B, 2A/B) NSCLC. Current waiting times for surgical resection of early stage NSCLC at UHN ranges from 4 to 6 weeks (Hui, Johnston et al. 2004), thus patients would not experience significant delay in time to surgery through this trial design. This study provides the opportunity to explore the impact of erlotinib on early stage NSCLC in humans, with pharmacodynamic assessment expected in 100% of patients post-treatment, in addition to correlative imaging. This study will evaluate the feasibility of preoperative therapy with erlotinib, and may facilitate the identification of predictive markers for response to erlotinib in early stage NSCLC. This may help further define the subset of patients who would benefit from adjuvant EGFR tyrosine kinase inhibitors, and those who may require other adjuvant approaches including chemotherapy and further clinical trials.