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A. Gu



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    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.12-001 - Erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) with activating Epidermal Growth Factor Receptor (EGFR) mutation (NCT01217619, EASTERN): study update (ID 260)

      09:30 - 09:30  |  Author(s): A. Gu

      • Abstract

      Background
      Approximately 15% of patients with NSCLC are diagnosed with stage IIIA-N2 disease, the treatment modalities of which are not clearly defined due to its heterogeneous character. Patients with stage IIIA N2 NSCLC have poor outcomes with 5-year survival rate of approximately 15% after treatment with surgical resection or chemo-radiotherapy. Tyrosine kinase inhibitor mono-therapy as the first line treatment could significantly improve tumor response rate and disease progression free survival (PFS) for metastatic NSCLC patients with activating EGFR mutation. The objective of this trial is to explore the efficacy and safety profile of erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with activating EGFR mutation.

      Methods
      This is a prospective, single arm, phase Ⅱ clinical trial. Patients with Endobronchial Ultrasound(EBUS) confirmed stage ⅢA-N2 NSCLC with activating EGFR mutation in exon 19 or 21 will be enrolled into the study. All the recruitment patients will be treated by erlotinib 150mg orally per day for 56 days for neoadjuvant period. Patients will be assessed after erlotinib treatment and those who get response from neoadjuvant therapy and are technically resectable will undergo surgery treatment. The adjuvant regime is decided by the investigator taking patients’ benefits into consideration. The primary endpoint is radical resection rate. The secondary endpoints are pathological complete resection rate(pCR), objective response rate(ORR), disease free survival(DFS), overall survival(OS), quality of life(QoL) and safety profile. Patients after surgery and therapy will receive long-term follow-up including regular chest CT and ultrasound examination.

      Results
      Eighty-eight(88) patients have been screened and 15 patients have been enrolled since first patients in (FPI) on 30th April, 2011. Excluded reasons including ineligible pathological diagnosis (n=23), ineligible stage (n=36), without EGFR mutation (n=10) and poor compliance (n=4). Ineligible stage including T1-3N0M0 (n=11), T1-3N1M0 (N=8), T1-3N3M0 (N=8), T1-3N2M1 (N=7) and T4N2M0 (N=2). 41% patients who were diagnosed with stage IIIA-N2 non-small cell lung cancer when in chest CT examinations were not in the stage after endobronchial ultrasound(EBUS) , and became the main reason for screening failure in this study. Seven patients had partial response, 3 patients with stable disease and 2 patients were still on treatment (DCR 66.6%). 3 patients with progress disease. Due to active hepatitis and technical infeasibility, 2 patients with partial disease didn’t receive surgery. However, one stable disease patient and five partial response patients (40%) received R0 surgery.

      Conclusion
      Neoadjuvant erlotinib therapy might be a promising treatment for IIIA-N2 NSCLC patients with EGFR activating mutation. EBUS helps the judgment of mediastinal lymph node metastasis and is better than CT scan.

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    P3.05 - Poster Session 3 - Preclinical Models of Therapeutics/Imaging (ID 159)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.05-006 - Inhibition of Tumor Cell Growth, Migration by SIM-89, a Novel Inhibitor of c-Met Tyrosine Kinase (ID 1112)

      09:30 - 09:30  |  Author(s): A. Gu

      • Abstract

      Background
      It has been found that HGF-dependent c-Met（HGFR） autocrine is activated in a wide variety of human primary and second malignancies. On the other hand, the metastatic growth potential of tumors can be activated through paracrine mechanism. c-Met dysregulation leads to lung cancer development through overexpression and mutation.

      Methods
      70 kinase enzymogram screening was proceeded by Z-lyte technique. MOA analysis was completed on the inhibited kinases. Cell vitality was determined at 24h, 48h, 72h after treatment through CCK8 method. Transwell system was used to observe the inhibition of cell migration. Difference of special gene expression was evaluated by Real-time PCR. Westernblot assay was used to compare the expression difference of c-MET and p-MET. HGF level in culture medium is determined by ELISA.

      Results
      SIM-89 can inhibit 3 kinases including c-Met（IC50=297nM）, AMPK, TRKA (IC50=150.2nM). SIM-89 has an ATP competive inhibition on c-Met. By Real-time PCR, SIM-89 has been found to inhibit STAT1, JAK1, c-Met gene expression in H460 cell. P-Met expression of A549, H441, H1299 and B16F10 cell can be inhibited by SIM-89. HGF level of supernatant in culture is significantly lower than control group. Vitality of NSCLC cell lines is inhibited dependent on time and concentration by SIM-89. Induced by HGF, migration of H460, H1299 cell is inhibited.

      Conclusion
      SIM-89 has significant inhibitive effect on c-Met, TRKA kinases. It also can inhibit proliferation, migration and HGF autocrine of NSCLC cell significantly. Further study in vivo should be carried to explore the pharmacokinetics of SIM-89.