Author of

• 20156

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  P1.07 - Immunology and Immunotherapy (ID 693)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Immunology and Immunotherapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22691

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    P1.07-023 - The Correlation Between B7-H4 Expression and Survival of Non-Small Cell Lung Cancer Patients Treated with Nivolumab (ID 9569)

    09:30 - 09:30  |  Author(s): P. Bruzzi
    • Abstract

    Background:
    In spite of the results achieved by nivolumab in advanced non-small cell lung cancer (NSCLC), reliable predictive factors are still needed, and even the expression of the programmed death protein 1 ligand (PD-L1) has a limited role in predicting benefit from this agent. Our aim was to determine whether the expression of other molecules involved in immune response might be associated with outcomes of NSCLC patients receiving nivolumab.
    
    Method:
    This retrospective study included patients treated with nivolumab for advanced NSCLC (Nivolumab Cohort). Response rate (RR) and progression-free survival (PFS) were assessed by response evaluation criteria in solid tumors (RECIST) v 1.1 and immune-related response criteria (irRC). Available tumor specimens were analyzed by immunohistochemistry (IHC) in order to determine the expression of PD-L1, PD-1 ligand 2 (PD-L2), PD-1, B7-H3, and B7-H4. The possible correlations between IHC findings and clinical outcomes were explored. Additionally, the meaningful biomarkers observed in the Nivolumab Cohort were assessed in a population of NSCLC patients treated with platinum-based chemotherapy (Chemotherapy Cohort) and the results from the two cohorts were compared in order to determine whether the administered treatment played a role in our observations.
    
    Result:
    The Nivolumab Cohort included 46 evaluable patients. The following proportions of positive IHC samples were observed: PD-L1=15.22%; PD-L2= 17.39; PD-1= 67.39%; B7-H3= 13.04%; B7-H4= 36.96%. At univariate analysis, patients expressing B7-H4 ≥1% had significantly lower PFS compared to those patients with B7-H4 <1% according to RECIST (1.67 vs. 2.00 months; p= 0.026) and irRC (1.73 vs. 2.17 months; p= 0.039), as well as a numerically lower overall survival (OS; 4.37 vs. 9.83 months; p= 0.064). At multivariate analysis for OS, PD-L1 ≥1% had favorable effect (HR= 0.29; p= 0.027), while B7-H4 ≥1% had unfavorable effect (HR= 2.98; p= 0.006). No other correlation was observed in this cohort. Within the Chemotherapy Cohort (n=27), no significant correlation between IHC findings and response or survival was observed. At the multivariate analysis including both cohorts, a statistically significant interaction was observed between OS and the combined effect of B7-H4 expression and treatment (p= 0.048), favoring nivolumab in B7-H4 <1% patients (HR= 0.60) and chemotherapy in B7-H4 ≥1% patients (HR= 0.67).
    
    Conclusion:
    A meaningful negative correlation between B7-H4 expression and outcomes was observed with nivolumab, but not with chemotherapy. In spite of a relatively small patient population, our results strongly encourage further studies exploring the potential role of B7-H4 as predictor of outcomes during treatment with nivolumab.