Virtual Library

Start Your Search

M.A. Molina-Vila



Author of

  • +

    Targeted therapies and management of brain metastasis (ID 40)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • +

      3O - Innate resistance in EGFR mutant non-small cell lung cancer (NSCLC) patients by coactivation of receptor tyrosine kinases (RTKs) (ID 339)

      16:45 - 18:15  |  Author(s): M.A. Molina-Vila

      • Abstract
      • Slides

      Background:
      The MET ligand hepatocyte growth factor (HGF) in stromal cells provides an alternative signaling mechanism for EGFR by inducing inter-receptor cross talk with EphA2, CUB domain-containing protein-1 (CDCP1) or AXL. Src-homology 2 domain-containing phosphatase 2 (SHP2) also plays a role in RTK signaling and is required for MAPK activation.

      Methods:
      We studied the expression levels of stromal HGF and tumor RTKs: AXL, CDCP1, MET, and EphA2, as well as SHP2, and clinical outcome in baseline samples of 64 EGFR-mutant NSCLC patients (pts) treated with first-line EGFR TKI. Paraffin-embedded samples and the discrimination between tumor and stromal cells were performed by a pathologist. mRNA expression was analyzed by qRT-PCR.

      Results:
      AXL and CDCP1 were among the genes that most significantly influenced treatment outcome. Median progression-free survival (PFS) was 14 months (mo) and 23.4 mo for pts with high and low AXL mRNA, respectively (p = 0.03), (HR: 2.05, p = 0.03). Median PFS was 9 mo and 20.2 mo for pts with high and low CDCP1 mRNA, respectively (p = 0.01), (HR: 2.1, p = 0.02). There were no significant differences in PFS according to levels of EPHA2 and MET in the tumor, and HGF in the stroma. Median PFS was 11.4 mo and 24 mo for pts with high and low SHP2 mRNA, respectively (p = 0.09) (HR: 2.4, p = 0.01). Median overall survival (OS) was 19.1 mo and 40.7 mo for pts with high and low AXL mRNA, respectively (p = 0.009) (HR: 2.9, p = 0.001). Median OS was 19.1 mo and 34.9 mo for pts with high and low CDCP1 mRNA, respectively (p = 0.03) (HR: 2.2, p = 0.03). In addition, differences in OS were noted according to levels of EPHA2, MET and SHP2.

      Conclusions:
      AXL and CDCP1 are adverse predictive markers of PFS and OS. It has been reported that overexpression of several RTKs can substitute EGFR signaling in EGFR mutant NSCLC pts. The findings show the need to scrutinize RTK levels in EGFR mutant NSCLC patients and, henceforth, the importance of tailored combinatory therapy with AXL inhibitors, or with Src inhibitors, in those pts with elevated CDCP1 (CDCP1 triggers SFK activation).

      Clinical trial identification:


      Legal entity responsible for the study:
      Institut d’Investigació en Ciències Germans Trias i Pujol, Badalona, Spain Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain

      Funding:
      Institut d’Investigació en Ciències Germans Trias i Pujol, Badalona, Spain Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain

      Disclosure:
      All authors have declared no conflicts of interest.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.