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Lauren Chiec



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    MA19 - Genomic Markers of IO Response (ID 922)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
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      MA19.04 - The Clinical Implication of Frameshift Indel Mutation Burden in Non-Small Cell Lung Cancer (NSCLC) (ID 12592)

      15:35 - 15:40  |  Author(s): Lauren Chiec

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor mutational burden (TMB) has been proposed as a potential predictive marker for immune checkpoint inhibitor (ICI) response in many cancers, including NSCLC. Recently, research has revealed frameshift indel (fsindel) of all mutations to be significantly associated with ICI response in melanoma patients. However, little is currently known regarding its clinical implication in NSCLC patients treated with PD1/PD-L1 inhibitors (ICIs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Next generation sequencing of 324 genes (FoundationOneTM) was used to derive fsindel burden and TMB. A total of 128 patient data with NSCLC treated with ICIs were analyzed from Northwestern University (N=68) and the University of Miami (N=60). A total of 128 patients were divided into two groups with 0 fsindel (FS-) and more than 1 fsindel (FS+). Progression free survival (PFS) and overall survival (OS) were compared between FS+ and FS- groups. PFS and OS outcomes of TMB high group (H-TMB, upper¼) and TMB low group (L-TMB, lower¼) were also compared.

      4c3880bb027f159e801041b1021e88e8 Result

      figure 1.jpg

      Among 128 patients, 51.6% belonged to FS+ group (N=66). Between FS-/FS+ groups, there were no significant differences in mean age (66.2/66.0) and performance status (0.9/0.9). Lines of ICIs used in the FS-/FS+ groups were 1st (19/19%), 2nd (47/56%), 3rd (24/11%), and 4th line or more (10/14%). FS+ group had significantly longer PFS compared with FS- group (median 6.2/2.7 months, P=0.02, Figure 1). No significant difference in OS was seen between the two groups (median 16.8/11.2 months, P=0.70). In contrast, however, H-TMB did not show any significant difference in PFS (median 5.6/4.0 months, P=0.14) and OS (median 15.8/15.1 months, P=0.69) compared to L-TMB.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first report to illustrate an association between fsindel and outcome in patients with NSLC treated with ICIs. Our findings suggest its potential role as a predictive marker for immunotherapy.

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