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Tianwei Xu



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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
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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): Tianwei Xu

      • 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 (1st-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 1st-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

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-106 - Real-World Data to Evaluate the Clinical Benefit of NGS for Directing Lung Adenocarcinoma Treatment (ID 12870)

      12:00 - 13:30  |  Author(s): Tianwei Xu

      • Abstract
      • Slides

      Background

      Since mid-2017, multiple NGS-based companion diagnostic tests have been approved in NSCLC to select patients eligible for targeted therapy and immunotherapy. Here, we retrospectively analyzed the benefit of NGS for advanced lung adenocarcinoma in routine clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From 2016 to 2018, the samples taken from 9 lung adenocarcinoma patients were sent to Geneplus-Beijing Institute for genetic testing. Mutation profiles were analyzed using hybridization capture based NGS, which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes). The tumor response was evaluated using RECIST v1.1.

      4c3880bb027f159e801041b1021e88e8 Result

      Six tumor tissue samples, two blood samples and one pleural effusion sample were analyzed (Table 1). No actionable mutation was detected in patient 1 and then he left hospital without additional treatment. The KRAS mutation present in patient 2 suggested that he might be resistant to EGFR-TKIs. Therefore, he received chemotherapy. According to the genetic testing results, all the other patients received EGFR-TKIs and the disease control rate was 100% at the 2nd month. Apart from EGFR T790M mutation, EGFR amplification was present in patient 8 with disease progression following gefitinib therapy. She received osimertinib and achieved PR at the 2nd month. The response has maintained for over 7 months up to now, which made us reconsidering the controversial correlation between EGFR amplification and EGFR-TKI effectiveness. Rare EGFR mutation and MET amplification were detected in patient 9, and then he was treated with icotinib.The best response was SD at the 4th month. However, he died of pulmonary embolism or cerebral infarction, making the duration of response 4 months.

      Table 1. Clinical and genetic characteristics of 9 patients   
      Patient No Age/Gender Sample Previous Targeted Therapy Actionable Mutations Following Treatment Response Evaluation (2nd month) Duration of response (months)
      1 72/Male Blood No No No treatment Not applicable Not applicable
      2 62/Male Tissue No KRAS p.G12A, STK11 p.D53Gfs*110 Chemotherapy Not available Not available
      3 62/Male Tissue No EGFR p.L747_T751del (EX19del) Gefitinib PR 20+
      4 63/Female Tissue No EGFR p.L858R (EX21) Gefitinib PR 5+
      5 75/Female Tissue No EGFR p.L858R (EX21) Icotinib SD 11+
      6 63/Male Blood Icotinib EGFR p.L858R (EX21),CHEK2 c.445-1G>A Combined gefitinib and bevacizumab SD 6+
      7 79/Male Tissue No EGFR p.L747_T751del (EX19), NF1 c.587-1G>C, ATM c.2124+1G>T Gefitinib PR 2+
      8 80/Female Pleural effusion Gefitinib EGFR p.L858R (EX21), EGFR p.T790M (EX20), EGFR amplification Osimertinib PR 7+
      9 81/Male Tissue No EGFR p.G719A (EX18), MET amplification, CDK4 amplification Icotinib SD 4
      8eea62084ca7e541d918e823422bd82e Conclusion

      NGS-based genetic testing comprehensively predicts the effectiveness of targeted therapy. It can be widely used in routine clinical practice.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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