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J.S. Lee



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    P2.06 - Poster Session with Presenters Present (ID 467)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
    • Presentations: 1
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      P2.06-017 - Amethyst NSCLC Trial: Phase 2 Study of MGCD265 in Patients with Advanced or Metastatic NSCLC with Activating Genetic Alterations in MET (ID 5384)

      14:30 - 14:30  |  Author(s): J.S. Lee

      • Abstract
      • Slides

      Background:
      MGCD265 is a potent, orally available, small molecule RTK inhibitor of MET and Axl, both of which mediate signals for cell growth, survival, and migration. The Amethyst NSCLC trial is designed to evaluate the activity of MGCD265 in patients with NSCLC exhibiting genetic alterations involving MET. Alterations in MET, including gene amplification and/or genetic mutations, occur in approximately 7% of NSCLC cases converting MET to an oncogene capable of driving cancer development and progression. Amplification of MET has been associated with a poor prognosis in NSCLC. In addition, various genetic mutations result in the deletion of exon 14 in MET mRNA (METex14del) and the subsequent loss of the Y1003 regulatory binding site for CBL ubiquitin ligase, required for MET degradation and signal attenuation. Loss of the Y1003 binding site of MET results in sustained MET signaling, which has been implicated as an oncogenic driver in a subset of NSCLC. The importance of MET as a driver is demonstrated in xenograft models of NSCLC with METex14del and MET amplification, and where MGCD265 induces tumor regression. Additionally, confirmed partial responses have been observed in pts with NSCLC characterized by METex14del who were treated with MGCD265 in the Phase 1 setting.

      Methods:
      Pts with platinum pre-treated NSCLC characterized by activating genetic MET alterations identified in tumor tissue or circulating tumor DNA (ctDNA) are eligible for this multi-center, global, Phase 2 trial. Pts are assigned to one of four cohorts based on the type of MET dysregulation and detection method: 1) mutations in tissue, 2) amplification in tissue, 3) mutations in ctDNA, and 4) amplification in ctDNA. The primary endpoint is Objective Response Rate (ORR) in accordance with RECIST 1.1; a Bayesian Predictive Probability Design is applied independently to each cohort. Secondary objectives include safety, tolerability, response duration, survival, correlation between tissue and ctDNA testing, and PK/PD. This study is currently open globally, and recruitment is ongoing.

      Results:
      Section not applicable.

      Conclusion:
      Section not applicable.

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    P3.02a - Poster Session with Presenters Present (ID 470)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02a-018 - Efficacy of Pemetrexed Based Chemotherapy Compared with Non-Pemetrexed Based Chemotherapy in Advanced, ALK-Positive NSCLC (ID 5555)

      14:30 - 14:30  |  Author(s): J.S. Lee

      • Abstract

      Background:
      Previous retrospective studies suggested that lung cancer patients with anaplastic lymphoma kinase (ALK) gene rearrangements are associated with sensitivity to pemetrexed chemotherapy. To determine the efficacy of pemetrexed based chemotherapy compared with non-pemetrexed based chemotherapy, we retrospectively evaluated clinical outcome in ALK positive non-small cell lung cancer (NSCLC) patients.

      Methods:
      We identified 126 patients with advanced, ALK-positive NSCLC who received 1st line cytotoxic chemotherapy from Seoul National University Hospital and Seoul National University Bundang Hospital. We compared response rate, progression-free survival, and overall survival according to chemotherapy regimens. We also analyzed the intra-cranial time to progression and proportion of ALK-positive cells as a predictive factor of pemetrexed efficacy.

      Results:
      Forty eight patients received pemetrexed based chemotherapy and Seventy eight patients received non-pemetrexed based chemotherapy as first line systemic treatment. One hundred eighteen patients received platinum double combination chemotherapy. The pemetrexed based chemotherapy group shows superior overall response rate (44.7% versus 14.3%, p<0.001) and disease control rate (85.1% versus 62.3%, p=0.008). Pemetrexed based chemotherapy group had longer progression free survival (6.6 months versus 3.8 months, p<0.001). Exposure to pemetrexed and exposure to second generation ALK inhibitor were independent prognostic factors of overall survival (p=0.016 and p=0.011, respectively). Intra-cranial time to progression (TTP) was similar among treatment group (32.7 months versus 35.7 months, p= 0.733). Proportion of ALK positive cells was not statistically significant predictive factor of survival in pemetrexed based chemotherapy.

      Conclusion:
      Pemetrexed based regimen may prolong progression free survival compared with other regimens in ALK positive NSCLC in the first line setting. Exposure to pemetrexed is associated with improved survival compared with that of premetrexed-naive controls in ALK positive NSCLC.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-061 - Neutrophil/Lymphocyte Ratio Predicts the Efficacy of Anti-PD-1 Antibody in Patients with Advanced Lung Cancer (ID 4974)

      14:30 - 14:30  |  Author(s): J.S. Lee

      • Abstract

      Background:
      Therapeutic antibodies to programmed death receptor 1 (PD-1) have shown clinical activity in lung cancer. The aim of this study is to investigate the clinical factors, including inflammatory markers such as neutrophil/lymphocyte ratio (NLR), to predict response to anti-PD-1 antibody in advanced lung cancer patients.

      Methods:
      We retrospectively analyzed 51 patients who had advanced lung cancer and had been treated with anti-PD-1 antibodies between 2013 and 2015. The values of NLR were assessed at two time points: at baseline (pre-treatment) and at 6 week after the start of treatment (post-treatment). NLR of 5 was used as the cutoff value.

      Results:
      The median age of the patients was 68 years; 76.5% were male, and 27.5% were never smokers. Most patients had adenocarcinoma (n = 28); 17 had squamous cell carcinoma, and 6 had others. Eighteen of 51 patients (35.3%) had clinical objective response to anti-PD-1 antibody. Non-adenocarcinoma histology and low post-treatment NLR was significantly associated with clinical response, while gender, smoking history, line of treatment and pre-treatment NLR were not predictive of response. Liver metastasis, brain metastasis, and high post-treatment NLR were significantly associated with worse tumor response. Patients with a high post-treatment NLR had significantly shorter PFS (median 1.3 months vs. 6.1 months, p < 0.001). Multivariable analysis demonstrated that high post-treatment NLR (hazard ratio [HR] 20.1, 95% confidence interval [CI] 5.5 - 73.9, p < 0.001), presence of liver metastasis (HR 5.5, 95% CI 2.1 - 14.6, p = 0.001), and CNS metastasis (HR 2.9, 95% CI 1.1 - 7.4, p = 0.027) were independent predictive factors for short PFS. Figure 1



      Conclusion:
      Clinical factors including post-treatment NLR at 6 week might be predictive of clinical benefits from anti-PD-1 antibody therapy in lung cancer.