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N. Mohindra



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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  |  Author(s): N. Mohindra

      • 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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