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: 2
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22692

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    P1.07-024 - ISEND May Predict Clinical Outcomes for Advanced NSCLC Patients on PD-1/PD-L1 Inhibitors but<br /> Not Chemotherapies or Targeted Kinase Inhibitors (ID 9586)

    09:30 - 09:30  |  Author(s): V. Florou
    • Abstract

    Background:
    We have shown that the iSEND model may be predictive of clinical outcomes for advanced NSCLC (aNSCLC) patients receiving nivolumab but little is known of its potential performance for patients on other PD-1/PD-L1 inhibitors (PD-1/PD-L1i), chemotherapies (Chemo) or Targeted Kinase Inhibitors (TKIs).
    
    Method:
    We evaluated clinical outcomes of 325 aNSCLC patients who received second-line PD-1/PD-L1i (nivolumab, pembrolizumab, or atezolizumb, n=203), first-line platinum followed by maintenance (Chemo, n=81), and TKIs (erlotinib, afatinib, or crizotinib, n=41). As described in our previous reports, the iSEND model (Sex, ECOG [Performance status], NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR = NLR after treatment - pretreatment NLR]) was developed. We stratified each treatment group by iSEND and compared progression free survivals (PFS) and clinical benefit rates (CBR) at 12+/-2 weeks in the iSEND Good vs. the iSEND Others (Intermediate and Poor).
    
    Result:
    Median follow-up was 9.5 (95% CI: 7.1-11.9), 11.7 (95% CI: 4.5-18.9) and 9.3 months (95% CI: 4.5-14.2), respectively for PD-1/PD-L1i, Chemo, and TKIs groups. In the PD-1/PD-L1i group, PFS was better in the iSEND Good than the iSEND Others with a median of 17.4 vs. 5.1 months, (HR: 0.32, 95% CI, [0.20-0.50], p<0.0001) (Figure 1). In contrast, PFS was not better in the iSEND Good in Chemo (HR, 0.69, 95% CI, [0.42-1.20], p=0.19) or TKIs (HR, 0.89, 95% CI, [0.43-1.84], p=0.75). The area under the curves (AUC) of the iSEND for CBR at 12+/-2 weeks for aNSCLC patients treated with PD-1/PD-L1i was 0.72, (95% CI: 0.65-0.79, p<0.0001). The AUCs of iSEND for CBR in Chemo and TKIs were not significant. Figure 1. Kaplan-Meier curves for PFS in PD-1/PD-L1i, Chemo, and TKIs stratified by iSEND Good vs. Others Figure 1
    
    
    
    Conclusion:
    In our single-institution retrospective cohort, the iSEND model showed a predictive potential for advanced NSCLC patients treated with PD-1/PD-L1i but not for those treated with Chemo or TKIs
    
    

  • 22693

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    P1.07-025 - Correlating ISEND and Tumor Mutation Burden (TMB) with Clinical Outcomes of Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients on Nivolumab (ID 9587)

    09:30 - 09:30  |  Author(s): V. Florou
    • Abstract

    Background:
    We developed an algorithmic model namely, the iSEND (Sex, ECOG performance status, NLR [Neutrophil-to-Lymphocyte Ratio] & DNLR [Delta NLR =NLR posttreatment - pretreatment NLR]) to predict the clinical outcomes of aNSCLC patients receiving nivolumab. Performance of the iSEND has not been compared with other potential immunotherapy biomarkers like TMB.
    
    Method:
    We identified 36 aNSCLC patients who received nivolumab after platinum with commercial TMB reports. As described in our previous reports, the iSEND was used to categorize patients into good, intermediate, and poor groups. 36 matched patients were also categorized into high TMB: ≥ 20 m/Mb (mutations per megabase), intermediate TMB: 6-19 m/Mb, and low TMB: ≤5 m/Mb. We evaluated progression free survival (PFS), and overall survival (OS). Performances of the iSEND and TMB were correlated with clinical benefit at 12+/-2 weeks by receiver operating characteristic (ROC) curves.
    
    Result:
    The median follow-up was 18.4 months (95% CI: 10.1-26.7). There were 16 deaths. The number of patients from iSEND good, intermediate, and poor groups were 12 (33%), 18 (50%), and 6 patients (16%), respectively. The median overall survivals of iSEND good, intermediate, and poor groups were 15.7 (10.8-20.58), 10.3 (4.8-15.7), and 3.7 (0-7.8) months, respectively (p=0.00006). The median overall survivals for high, intermediate, and low TMB groups were unreached, 10.3 (4.7-15.9), and 12.4 (7.1-17.7) months, respectively. (p=0.211, Figure1) The area under ROC curve of the iSEND for clinical benefit at 12+/-2 weeks was 0.733 (p=0.025, 95% C.I.: 0.56-0.90). Four intermediate iSEND patients who had OS less than 6 months had low TMBs. Figure 1. Kaplan-Meier curves for Overall Survival by iSEND model and TMBFigure 1
    
    
    
    Conclusion:
    From a limited retrospective single institutional database, iSEND characterized the clinical outcomes of aNSCLC patients on nivolumab well and high TMB correlated with better outcomes. A larger cohort validation is encouraged to explore the mutual supplementary benefit for improved performance.