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Séverine Martinez



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    MA16 - Novel Mechanisms for Molecular Profiling (ID 917)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 203 BD
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      MA16.09 - Feasibility, Clinical Relevance of ALK/ROS1 Fusion Variant Detection by Liquid Biopsy in Advanced Non-Small Cell Lung Cancer (ID 13492)

      14:30 - 14:35  |  Author(s): Séverine Martinez

      • Abstract
      • Presentation
      • Slides

      Background

      Liquid biopsy offers an alternative non-invasive approach to reflect the tumor genomic landscape of NSCLC patients; however, the potential of liquid biopsies for ALK/ROS1 fusion detection is poorly described. Herein, we evaluated an amplicon-based NGS assay for ctDNA detection of ALK and ROS1 fusions in a large cohort of ALK and ROS1 NSCLC patients and correlation of variants with clinical data.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      ALK- and ROS1-translocated advanced NSCLC patients, were prospectively enrolled from October 2015 to April 2018 in 9 French institutions. ALK or ROS1 positivity was as confirmed by immunochemistry and FISH or RNAseq. ALK (EML4 variants v1, v2, v3), ROS1 (CD74, SLC34A2, SDC4 and EZR) fusions, and mutations in a panel of 36 NSCLC-associated genes were investigated in ctDNA using InVisionFirst™ (Plagnol V PLoS ONE, 2018).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 120 patients were included: 96 ALK and 24 ROS1. 30 samples were collected from patients who were TKI-treatment-naive, 257 during follow-up and 73 at progressive disease (PD) under TKI. The median age was 55 years-old (range 23-75); most patients were female (57%) and had a non-smoking history (59%). At diagnosis, 20% of patients presented with brain metastasis. All patients received at least 1 ALK-TKI (median: 1.6; range:1-6).

      Preliminary results are available for the first 54 patients: 21 at diagnosis and 33 at PD under TKI. ALK/ROS1 fusions were detected in 13/21 patients (62%) at diagnosis: 12/20 ALK-fusions (7 v1, 2 v2 and 3 v3) and in 1/1 ROS1-fusion (CD74-ROS1). No fusion was detected in 8 patients, which may be due to partner genes or variants not covered by this panel. However, 5 of these 8 patients had exclusive thoracic or brain PD.

      Liquid biopsies collected at the radiographic evaluation under therapy revealed complete ctDNA clearance of the fusion when patients experienced PR (n=4). In samples at PD, fusion was detected in 44% of patients (24/55) with evidence of acquired resistance in patients both positive and negative for fusion.

      Results for the remaining samples, correlation between fusion variant and survival, fusion variant and mechanism of resistance will be presented at the Congress.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that ctDNA profiling is a promising non-invasive tool for identification of ALK/ROS1 fusions and monitoring of response in advanced NSCLC patients. Systematic identification of the fusion partner may help to better understand the heterogeneity and evolution (sensitivity profile to targeted inhibitors and associated-mechanisms of resistance) of NSCLC driven by ALK and ROS1 rearrangement.

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