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Michele Simbolo



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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
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      P2.04-12 - A Genomic Signature [JAK2, JAK3, PIAS4, PTPN2, STAT3, IFNAR2] Predicts Baseline Resistance to Nivolumab in Advanced NSCLC. (ID 13459)

      16:45 - 18:00  |  Author(s): Michele Simbolo

      • Abstract
      • Slides

      Background

      With the exception of PD-L1 expression for pembrolizumab, no biomarkers allow to maximize the benefit of immunotherapy in advanced pretreated non-small-cell lung cancer (AP-NSCLC). The genomic abnormalities of genes involved in immune-escape/editing are suggested as baseline mechanisms of resistance.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A retrospective series of AP-NSCLC patients (pts) undergone Nivolumab (NIVO) was collected. FFPE-tumor blocks were analyzed to identity somatic mutations (SMs)/ copy number variations (CNVs) with a Ampliseq CGS panel (17 genes: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3 and TYK2). End-points were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).

      4c3880bb027f159e801041b1021e88e8 Result

      Data from 24 consecutive AP-NSCLC pts who received NIVO were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIVO [70.8%], median follow-up 6.8 months [range 1-23], deaths 14 [58.3%], male/female 79.2/20.8%, squamous/non-squamous 41.7/58.3%, EGFR mutant 5 [20.8%]). ORR (partial) was obtained in 4 pts (16.6%, 95% CI 1.7-31.6%), with stable- and progressive-disease in 5 (20.8%, 95% CI 4.5-37.1%) and 15 (62.5, 95% CI 43.1-81.8%) pts, respectively. JAK3/JAK2 (6/3 pts, 25/12.5%) CNVs, and IFNAR2/STAT3 SMs (2 pts, 8.3%) were the most frequent (>1 pts) abnormalities. The 12 pts with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 and JAK2/3 SMs/CNVs had a significantly lower median OS (4 months, 95% CI 1-8) and PFS (3 months, 95% CI 2-3.5) than the other 12 pts wild-type/other alterations (median OS 13 months, n.e.; median PFS 6 months 95% CI 5-9) [p=0.046 for OS, p=0.002 for PFS]. No objective responses were observed in the pts’ subgroup harboring the gene signature (p=0.09). At multivariate analysis, the genomic signature was independently associated with shorter OS (HR 2.20 95% CI 1.21-4.06, p=0.01) and PFS (HR 6.1 95% CI 2-18.7, p=0.001). No significant correlation between EGFR mutations and outcome was found.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite the small sample, the customized gene sequencing of few genes involved in immune-escape/editing is able to identify a pts’ subgroup of AP-NSCLC who appears to derive a lower benefit from NIVO, supporting intrinsic resistance. A larger prospective validation is planned.

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