Author of

• 12701

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  P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12716

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    P3.12-015 - Surgery for Early Non-Small Cell Lung Cancer with Preoperative Erlotinib (SELECT): A Correlative Biomarker Study (ID 2529)

    09:30 - 09:30  |  Author(s): A.G. Sacher
    • Abstract

    Background
    Erlotinib has demonstrated major activity in EGFR mutation positive NSCLC, but may also benefit those with wild type tumours. We conducted a single-arm trial of pre-operative erlotinib in early stage NSCLC to assess radiologic and functional response as well as correlation with known and investigational biomarkers.

    Methods
    Patients with clinical stage IA-IIB NSCLC received erlotinib 150 mg daily for 4 weeks followed by surgical resection. Tumor response was assessed using pre- and post-treatment CT and PET imaging. Tumor genotype was established using Sequenom MassARRAY analysis. EGFR, PTEN, cMET and AXL expression levels were determined by immunohistochemistry. Pre- and post-treatment circulating markers/ligands for EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) were measured by ELISA. Tumor MET copy number by FISH and VeriStrat® analysis of pre-treatment serum samples is ongoing. Secondary endpoints included pathological response, toxicity and progression-free survival.

    Results
    Twenty-five patients were enrolled; 22 received erlotinib treatment with a median follow up of 4.4 years (range 2.2 to 6.4 years). Histology was predominantly adenocarcinoma (15) with smaller numbers of squamous cell carcinoma (7). PET response (25% SUV reduction) was observed in 2 patients (9%), both with confirmed squamous carcinoma histology. All patients met criteria for stable disease by RECIST and several experienced minor radiographic regression with histologic findings of fibrosis/necrosis, including 2 with squamous histology. The presence of an EGFR activating mutation was detected in two adenocarcinoma cases; one patient experienced minor radiographic response to treatment (exon 19 deletion) and the other stable disease (L858R). High pre-treatment serum levels of TGF- α correlated with tumor growth or primary resistance to erlotinib therapy (p=0.04), whereas high post-treatment soluble EGFR levels correlated with tumor response (p=0.02). Expression of EGFR, PTEN, cMET and AXL did not correlate significantly with tumor response.

    Conclusion
    Erlotinib appears to demonstrate some activity in EGFR wild-type tumors including those with squamous histology. These findings support that certain EGFR wild-type patients may respond to EGFR TKIs. Further research is needed to characterize these patients and elucidate the predictive ability of potential biomarkers such as TGF- α, EGFR copy number and others.