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    FP07 - Pathology (ID 109)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP07.17 - The Impact of Blood Based Host Immune Profile to Identify Aggressive Early Stage NSCLC   (ID 3600)

      00:00 - 00:00  |  Author(s): James Orsini

      • Abstract
      • Presentation
      • Slides

      Introduction

      Early detection of non-small cell lung cancer (NSCLC) provides the greatest opportunity for a cure. However, even when NSCLC is identified early, 30-60% of patients diagnosed with stage I-IIIA disease will experience local and/or distant recurrences, respectively. More precise tools are needed to refine lung cancer staging and identify patients that have a more aggressive disease who may benefit from additional treatment or enhanced disease surveillance following curative intent. The Host Immune Classifier (HIC) is a clinically validated, blood-based proteomic test designed to identify an inflammatory disease state associated with aggressive cancer. Here we report the results of a prospectively designed observational study evaluating the ability of the HIC to predict the survival outcomes of patients with early stage NSCLC.

      Methods

      The INSIGHT study (NCT03289780) has enrolled over 3,500 patients with NSCLC, regardless of stage, at 33 sites throughout the U.S. All subjects are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C) prior to treatment initiation. An interim analysis of secondary and exploratory endpoints was performed after 12-18 months (mo) follow-up with the first 2,000 enrolled patients. We report the overall survival (OS) of HIC-defined subgroups comprising patients with stage I through stage IIIA (defined by the AJCC seventh edition staging system) NSCLC treated according to standard of care practice.

      Results

      At the time of database lock, 335 patients with newly diagnosed early stage NSCLC were included in the analysis. Disease stage at study entry was: 20% Stage IA (N=68, 3% HIC-C), 13% Stage IB (N=45, 11% HIC-C), 11% Stage IIA (N=37 (14% HIC-C), 13% Stage IIB (N=44, 21% HIC-C), 32% Stage IIIA (N=141, 34% HIC-C). Without biomarker stratification, landmark 15 mo OS was 85% (95% CI 78-90%) for patients with localized disease (Stage I-IIA) and 73% (95% CI 65-79%) for patients with regional disease (Stage IIB-IIIA), respectively. When patients with localized disease were evaluated with the HIC test, 15 mo landmark OS was significantly decreased for patients classified as HIC-C (HIC-C 55% (95% CI 23-78%) vs. HIC-H 87% (95% CI 80-92%), HR 3.68 (95% CI 1.38-9.87), p value 0.01). Similarly, 15 mo landmark OS for regionally advanced NSCLC was also significantly reduced for patients classified as HIC-C (HIC-C 60% (95% CI 45-72%) vs. HIC-H 79% (95% CI 70-85%), HR 1.77 (95% CI 1.02-3.06), p value 0.04). HIC remained prognostic for OS when adjusted for other covariates such as stage, ECOG performance status, histology, and treatment type in a multivariate analysis (HR of 1.89 (95% CI 1.15-3.12), p value 0.012).

      Conclusion

      The use of blood-based immune profiling may identify early stage lung cancer patients with aggressive disease that could potentially benefit from enhanced disease surveillance or additional treatment. Furthermore, the inclusion of blood-based biomarkers such as the HIC into the anatomic TNM staging system may help improve prognostication and aid in refining stage classification.

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    MA08 - Advances in Biomarkers for Immune Checkpoint Blockade and Targeted Therapy in Non Small Cell Lung Carcinoma (ID 166)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
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      MA08.03 - Immunotherapy Alone or with Chemotherapy in Advanced NSCLC? Utility of Clinical Factors and Blood-Based Host Immune Profiling (ID 1117)

      16:45 - 17:45  |  Author(s): James Orsini

      • Abstract
      • Presentation
      • Slides

      Introduction

      Immune checkpoint inhibitors (ICI) have revolutionized cancer care with greater overall survival (OS) in patients with advanced stage non-small cell lung cancer (aNSCLC). However, even for patients with good ECOG performance status (PS) 0-1 and high PD-L1 expression, the overall response rate to single-agent ICI in the treatment naïve population is only 45%. Combination treatments might increase efficacy but add toxicity and higher cost. Better predictors of response to treatment are needed to guide treatment decisions. A prospectively designed, observational study assessed the ability of clinical factors and a clinically validated, blood-based, host immune classifier (HIC) to predict ICI therapy outcomes.

      Methods

      Over 3,500 NSCLC patients at any stage and line of therapy across 33 US sites have been enrolled in the prospective observational study (NCT03289780) that assesses subject sera by the proteomic HIC test (HIC-Hot or HIC-Cold) prior to treatment initiation. An interim analysis was performed after 12-18 months follow-up with the first 2,000 enrolled subjects. The correlation of various factors, including PD-L1 expression, age, histology, PS, smoking history, gender and the HIC result, with OS of subjects receiving ICI alone (ICI, n=86) or in combination with platinum-doublet chemotherapy (ICI+PD, n=98) was assessed.

      Results

      In a real-world clinical setting, OS of subjects with newly diagnosed aNSCLC did not differ significantly between ICI and ICI+PD (median OS (mOS): 9.4 vs. 12.5 months, hazard ratio 0.80 [95% confidence interval: 0.54–1.19], P-value=0.28). Survival analysis for subjects receiving ICI indicated that HIC-Hot, better PS and younger age, but not high PD-L1 expression (either 50% or 90% cutoff) were significantly associated with longer OS according to univariate analyses (see table). When adjusted for covariates in a multi-variate analysis, HIC and age remained significant predictors of OS (p=0.0006 and p=0.005), while PS did not (p=0.40). For patients receiving ICI+PD, only high PD-L1 expression was significantly associated with increased OS. While HIC individually trended towards significance, its inclusion in a multi-variate analysis of gender, smoking history (ever vs. never) and PD-L1 expression (<50% vs. ≥50%) did not improve the fit, indicating that HIC is not independently associated with OS in subjects receiving ICI+PD (p=0.27).

      Association of selected clinical factors and HIC individually with OS of patients receiving ICI or ICI+PD.
      Treatment Type Univariates mOS Hazard Ratio
      (95% confidence interval)
      P-value
      ICI HIC-Cold (N=30)
      vs.
      HIC-Hot (N=56)
      2.2 months
      vs.
      16.3 months
      2.61
      (1.49-4.56)
      0.0008
      ICI PS 2+ (N=24)
      vs.
      PS 0-1 (N=62)
      4.2 months
      vs.
      16.3 months
      2.10
      (1.19-3.73)
      0.011
      ICI Age >65 years (N=48)
      vs.
      Age <65 years (N=38)
      6.7 months
      vs.
      not reached
      1.80
      (1.01-3.20)
      0.046
      ICI PD-L1 <50% (N=12)
      vs.
      PD-L1 ≥50% (N=74)
      10.1 months
      vs.
      9.3 months
      1.32
      (0.64-2.72)
      Not significant
      (0.45)
      ICI PD-L1 <90% (N=57)
      vs.
      PD-L1 ≥90% (N=29)
      8.0 months
      vs.
      9.4 months
      1.43
      (0.77-2.65)
      Not significant
      (0.25)
      ICI+PD PD-L1 <50% (N=59)
      vs.
      PD-L1 ≥50% (N=39)
      8.5 months
      vs.
      not reached
      2.02
      (1.08-3.77)
      0.028
      ICI+PD HIC-Cold (N=33)
      vs.
      HIC-Hot (N=65)
      7.0 months
      vs.
      17.3 months
      1.76
      (0.99-3.11)
      Not significant
      (0.053)
      ICI+PD PS 2+ (N=17)
      vs.
      PS 0-1 (N=81)
      8.5 months
      vs.
      16.0 months
      1.42
      (0.74-2.85)
      Not significant
      (0.33)

      Conclusion

      The HIC test provides clinically meaningful information in addition to currently utilized clinical factors to potentially help guide immunotherapy treatment decisions for patients with newly diagnosed aNSCLC. HIC stratified survival for patients receiving ICI but not ICI+PD, suggesting that patients classified HIC-Cold may benefit from addition of chemotherapy to ICI.

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