Author of

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  P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

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

  • 26990

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    P2.04-14 - Tumor Mutational Burden Assessed by a Targeted NGS Assay Predicts Benefit from Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer  (ID 14516)

    16:45 - 18:00  |  Author(s): Luca Quagliata
    • Abstract

    Background
    

    Immune checkpoint inhibitors (ICI) improve overall survival in non-small cell lung cancer (NSCLC) in the 2^nd-line setting and lead to prolonged disease control in a subgroup of patients (pts). Robust predictive biomarkers for ICI are highly desired. In an exploratory analysis of the CheckMate 026 study, high tumor mutation burden (TMB) assessed by whole-exome sequencing was associated with improved outcome of pts treated with nivolumab.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    From our institutional database, 41 pts with metastatic NSCLC were included in this study and identified as either having clinical benefit (CB; defined as complete/partial response (CR/PR) or stable disease (SD)) or having no clinical benefit. TMB was assessed using a targeted NGS assay that simultaneously detects variants in all coding regions / sequences of 409 cancer-related genes (Oncomine Tumor Mutation Load Assay, Thermo Fisher Scientific, Waltham, MA, USA). TMB values were normalized to tumor cell content. The correlation between TMB and CB rate was assessed. Mann-Whitney test was used and differences were considered significant at a p-value <0.05.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Of 41 pts (mean age 63.7 years), 73% were male, 87.8% smokers and 71% had adenocarcinoma histology. Nivolumab was the most frequently used ICI (70.7%), and it was most commonly used in the 2^nd-line setting (61.0%). PR was observed in 29.2% of patients, and SD in 14.6%. CB rate was 43.8%. The median number of genomic mutations per Megabase (Mb) was 8.81. In pts with CB, median TMB with 11.52 mutations per Mb was significantly higher than in pts without response to therapy (7.71 mutations per Mb; p=0.02).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    TMB as determined by a targeted NGS panel comprising the coding regions of 409 cancer-related genes can reliably predict clinical benefit from ICI. These results need further confirmation due to limited sample size of this study. We are currently analyzing a second independent cohort, and results will be presented during the meeting.

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