Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26907

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    P2.01-102 - Comprehensive Next-Generation Sequencing Guided Targeted Therapies Improve Clinical Outcomes of Lung Cancer Patients (ID 13445)

    16:45 - 18:00  |  Author(s): Dongqin Zhu
    • Abstract
    • Slides

    Background
    

    Next-generation sequencing (NGS) has been increasingly involved in the clinical decision-making of cancer care, the primary applications of which are the identification of sensitizing mutations for targeted therapies and drug-resistant mechanisms. Along with more clinical validations and approvals of several commercially available targeted NGS panels by FDA for mutation profiling, it has been debated that whether comprehensive NGS test should be used as a standard procedure in clinical practice.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    In this study, we recruited 24 patients with stage IV lung cancer. 22 of them are adenocarcinoma and the other 2 are small cell lung cancer and squamous cell carcinoma, respectively. Genomic DNA from 13 tumor tissues, and circulating tumor DNA from 8 pleural effusions and 3 plasma samples in each corresponding patient were collected and subjected to targeted-NGS covering 416 cancer-related genes and 16 genes frequently rearranged in solid tumors. Targeted therapy or chemo/radiochemotherapy was applied in clinical practice with the consideration of patients’ requests and their affordability due to financial barriers. Patients’ clinical outcomes were further evaluated.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Of all patients, 54% of them (n=13) were detected with sensitizing mutations that have targeted drugs available, including EGFR exon 19 deletion (n=2), L858R (n=2) and L861Q mutations (n=1), ALK fusion (n=1), ROS1 fusion (n=1), MET exon 14 skipping (n=1), as well as EGFR T790M (n=5) for 4 patients who had progressed on the first-generation tyrosine kinase inhibitors (1^st-gen TKI) and 1 TKI-treatment naive patient. 69% of patients (n=9) with actionable mutations were subjected to targeted treatment, while the other 31% patients (n = 4) were treated with chemotherapy or radiochemotherapy. Consistent with clinical validations, the overall survival (OS) of targeted-treatment group is better than the systematic treatment group. On the other hand, for patients without detectable actionable mutations (n=11), 64% of patients (n=7) were underwent chemotherapy, while the rest were treated with 1^st-gen EGFR TKI as requested by the patients. As expected, chemotherapy-treatment group had a similar OS as the TKI group. Collectively, patients with sensitizing mutations achieved significantly longer OS from the TKI treatments than those without actionable mutations (p=0.02).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our data demonstrated that the existence of sensitizing mutation is the determining factor for the treatment efficacy of targeted therapies. In the real world, NGS test can not only be involved into the decision-making for the first line treatment, but also be instructive for treatment changes after drug-resistance developed

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