Author of

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  P88 - Targeted Therapy - Clinically Focused - ROS1 (ID 265)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36591

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    P88.01 - Comprehensive Profiling of ROS1 Fusions in Chinese Non-Small Cell Lung Cancer Patients (ID 1464)

    00:00 - 00:00  |  Presenting Author(s): Hanlin Xu
    • Abstract
    • Slides

    Introduction
    

    The frequency of ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) fusion in non-small cell lung (NSCLC) cancers has been reported from 1% to 2%. Therapies that target NSCLC patients harboring ROS1 fusions have been approved by the US Food and Drug Administration. This study aimed to clarify the distribution and clinical characteristics of ROS1 fusions in a large Chinese NSCLC population.

    Methods
    

    Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples of 5962 Chinese NSCLC patients were collected for 450 cancer gene-targeted next-generation sequencing (NGS) assay in a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic variants including single nucleotide variations (SNV), short/long, insertion/deletions (Indel), copy number alterations and gene fusions were analyzed. Microsatellite instability (MSI) and tumor mutational burden (TMB) were assessed in all patients.

    Results
    

    In total, ROS1 fusions were found in 1.5% (92/5962) of Chinese NSCLC, which was comparable to previously reported prevalence. Mutation rates varied in different histological types: 1.7% in adenocarcinoma, 0.4% in squamous cell carcinomas, and 1.6% in others. Compared with ROS1 wildtype, patients with ROS1 fusions were younger (median age 60 vs 54 years, respectively, P<0.001). ROS1 fusion occurred more frequently in female (female 2.1% vs male 1.0%, respectively, P=0.001) and never-smokers (never smoker 2.0% vs smoker 0.6%, respectively, P=0.001) .The most common partner genes of ROS1 fusions were CD74 (41%), SDC4 (20%), EZR (18%), SLC34A2 (8%) and TPM3 (6%). Rare partners accounted for 7% in all cases with ROS1 fusions, and two novel partners, ATF3 and BTBD9 were identified. Tumors with ROS1 fusion had a lower median TMB than wild type (2.8 vs. 4.6 muts/Mb, P<0.001). Only one patient with ROS1 fusion was MSI-H status with slightly elevated TMB (12.3 muts/Mb).

    Conclusion
    

    ROS1 fusions were found in 1.5% of Chinese NSCLC patients, which occurred more frequently in younger patients, female and never-smokers. NGS is a reliable technique to assess ROS1 fusions, including both classic and rare ROS1 fusions.

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