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Matteo Brunelli



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-51 - A 6-Gene Immune Genomic Signature (IGS) Predicts Resistance to Nivolumab [NIV] in Advanced Pretreated NSCLC: Results of PRINCiPe Trial (ID 1885)

      10:15 - 18:15  |  Author(s): Matteo Brunelli

      • Abstract
      • Slides

      Background

      Genomic abnormalities detected in immune-escape/editing-related genes may promote immunotherapy resistance. In the light of this hypothesis, we designed the PRINCiPe (Predictors of Resistance to Immunotherapy with NIV) study in APNSCLC.

      Method

      FFPE-tumor blocks of APNSCLC pts undergone NIV were retrospectively sequenced for Somatic Mutations/Copy Number Variations (SM/CNV) (Ampliseq 17-genes customized panel: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3, TYK2). End-points of the PRINCiPe study were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).

      Result

      Forty-four APNSCLC pts were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIV [75.0%], male/female 77.3/22.7%, squamous/non-squamous 31.8/68.2%, EGFR mutant 5 [11.4%], median follow-up 6.8 months [range 1-23], deaths 24 [54.5%]). JAK3/JAK2 (7/3 pts, 15.9/6.8%) CNV and IFNAR2 SM (4 pts, 9.1%) were the most frequent (>1 pts) abnormalities. Pts (n=15) with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 SM and/or JAK2/3 CNV (IGS+) had a significantly lower PFS than those without (IGS-) (median PFS 2.8 vs. 6.6 months; p=0.006), while a trend towards significance was observed in terms of OS (median OS 5.1 vs. 13.0 months for IGS+ and IGS-, respectively; p=0.06 log-rank, p=0.05 Tarone-Ware). At multivariate analysis, IGS+ was independently associated with a shorter PFS (HR 2.64, 95% CI 1.3-5.4, p=0.008). IGS+ pts were significantly more probable to be affected by liver metastases than those without (p=0.01).

      Conclusion

      The identified IGS appears to select APNSCLC pts with a significant lower chance to benefit from NIV, supporting intrinsic resistance. A prospective larger and external validation is ongoing, as well as the comprehensive transcriptome analysis.

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