Abstract
Background: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers.Results: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent minor radiographic regression and histologic findings of fibrosis/necrosis including in squamous histology. Only two had EGFR mutations identified, one with minor radiographic response and the other stable disease after 4 weeks of EGFR TKI. High pre-treatment serum levels of TGF-α correlated with primary resistance to erlotinib (p = 0.02), whereas high post-treatment soluble EGFR levels correlated with response (p = 0.03). EGFR, PTEN, cMET and AXL expression did not correlate with tumor response.Methods: Clinical stage IA–IIB NSCLC patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor response was assessed using CT, PET and pathological response. Tumor genotype was established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was assessed by immunohistochemistry, circulating markers of EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by FISH.Conclusions: Erlotinib appears to demonstrate activity in EGFR wild-type tumors including squamous carcinoma. Further research is needed to characterize those wild-type patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others.
Highlights
First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have transformed the treatment of advanced non-small cell lung cancer (NSCLC) [1,2,3,4]
Further research is needed to characterize those wildtype patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others
The use of EGFR TKI remains controversial in patients with advanced EGFR wild-type NSCLC
Summary
First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have transformed the treatment of advanced non-small cell lung cancer (NSCLC) [1,2,3,4]. These agents represent the current standard of care for the treatment of EGFR mutant advanced NSCLC. The potential for EGFR TKI as adjuvant therapy has been investigated, but randomized trials to date have not demonstrated an overall survival benefit, even in the EGFR mutant NSCLC subgroup [8,9,10]. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers
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