A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer

Oncotarget. 2016 May 3;7(18):25632-9. doi: 10.18632/oncotarget.8350.


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.

Keywords: NSCLC; erlotinib; preoperative window study.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Chemotherapy, Adjuvant / methods
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Erlotinib Hydrochloride