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Young Kwang Chae



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    OA 07 - Biomarker for Lung Cancer (ID 659)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      OA 07.03 - Circulating Tumor DNA Mutant Allele Frequency and Tumor Burden as Biomarkers for Response to Immune Checkpoint Blockade (ID 9606)

      16:05 - 16:15  |  Presenting Author(s): Young Kwang Chae

      • Abstract
      • Presentation
      • Slides

      Background:
      Identifying biomarkers to select patients who respond to immune checkpoint blockade in non-small cell lung cancer (NSCLC) remains a challenge. Cell-free circulating tumor DNA (ctDNA) has emerged as a non-invasive, quantitative method of monitoring genomic alterations in the peripheral blood. We evaluated the clinical utility of ctDNA mutant allele frequency (MAF) and tumor burden based on imaging as biomarkers for response to immune checkpoint blockade in NSCLC.

      Method:
      From a cohort of 136 patients with ctDNA samples, 20 patients were retrospectively identified with ctDNA testing before initiation of anti-PD-1/PD-L1 treatment or within 90 days of therapy initiation. ctDNA testing was performed by Guardant360 (Guardant Health, Redwood City, CA). MAF of the dominant clone was identified quantitatively for each patient. In addition, baseline tumor burden was estimated using RECIST version 1.1. MAF and tumor burden were correlated with progression free survival (PFS) and overall survival (OS). Logistic regression of response rate (RR) and clinical benefit rate (CBR) was also performed.

      Result:
      Higher median ctDNA MAF was correlated with significantly shorter PFS and OS (hazard ratio (HR) 3.4, p=0.03 and HR 10.4, p=0.03, respectively) (Figure 1). There was no significant association between tumor burden estimation and PFS and OS. However, tumor burden was significantly correlated with MAF (r=0.58, p=0.007). MAF and tumor burden estimation did not correlate with RR or CBR in this small sample. Figure 1



      Conclusion:
      ctDNA MAF appears to be a promising, non-invasive, prognostic biomarker for response to immune checkpoint blockade in NSCLC with higher MAF associated with shorter PFS and OS. ctDNA MAF may also serve as a surrogate for tumor burden. Prospective studies with serial ctDNA sampling are necessary to further validate these findings.

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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
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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): Young Kwang Chae

      • 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