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Martin P Barr



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    P34 - Pathology - Liquid Biopsy (ID 104)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P34.01 - Utility of Assessment of the EGFR Resistance Genotype using Cell-Free DNA and CTCs from Liquid Biopsies   (ID 2321)

      00:00 - 00:00  |  Presenting Author(s): Martin P Barr

      • Abstract
      • Slides

      Introduction

      In advanced disease, the presence of an EGFR mutation confers a more favourable prognosis and strongly predicts for sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Clinical studies have demonstrated that ~20% of biopsies are inadequate for molecular testing due to insufficient tumour tissue. Tissue genotyping is further limited by often inaccessible tissue, heterogeneity and risks associated with serial tumour biopsies. More than 60% of patients who initially respond to EGFR TKI therapy develop resistance due to the emergence of the T790M or other resistance mutations. In this study, we hypothesise that concurrent assessment of circulating tumour cells (CTCs) and cell-free DNA (cfDNA) enhances assessment of EGFR resistance using the liquid biopsy as a non-invasive technology.

      Methods

      Patients with EGFR positive disease (n=21) were consented across three Irish Oncology Centres and stratified into cohort 1 (currently receiving EGFR TKI therapy) or cohort 2 (newly diagnosed, treatment-naïve patients to receive EGFR TKI therapy). Liquid (blood) biopsies were collected every 3 months over two years. Plasma genotyping of cell-free DNA was carried out using the FDA-approved Cobas® EGFR mutation test v2 (Roche Diagnostics) for the most common EGFR mutations across exons 18-21 of the EGFR gene. Analytical performance of the Cobas® EGFR mutation test was compared with two next generation sequencing (NGS) cell-free DNA panels (Oncomine & Avenio). In addition, the potential clinical utility of CTC numbers in monitoring response to therapy and the emergence of resistance (T790M) were assessed. CTCs were isolated from blood at each time-point using ScreenCell® size exclusion technology. Neutrophil to lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) were used as a measure of systemic inflammation and prognosis in this EGFR patient subset. Univariate Cox proportional hazards analysis was used for overall survival (OS) and time to progression (TTP).

      Results

      Plasma genotyping using the Cobas® EGFR mutation test identified Exon 19, L858R and L861Q mutations in 62%, 24% and 5% of liquid biopsy-derived cfDNA, respectively. The emergence of the T790M resistance mutation was detected in 57% of patients during treatment with EGFR TKIs. In contrast to cohort 2, patients in cohort 1 with a T790M had a worse OS and shorter TTP relative to patients with an EGFR sensitizing mutation. Using the Wilcoxon sign rank test, there were no significant correlations in EGFR mutation profile between the Cobas® mutation test and Oncomine (p=0.054) or Avenio (p=0.94) NGS panels. While there were no significant correlations between CTC numbers and T790M status in both cohorts, significant correlations were found between CTCs and WBC count (p=0.000073) and LDH (p=0.0010) in cohort 1 only. High CTC numbers correlated with a shorter TTP in both patient cohorts. This however was not statistically significant. Patients with T790M had a significant increase in inflammatory biomarkers (NLR, LDH, WBC) when examined across all time-points (p<0.05).

      Conclusion

      While larger prospective studies are warranted, these data add further knowledge to the use of cfDNA plasma genotyping and CTCs for the rapid detection of EGFR genomic alterations in patients with NSCLC during EGFR TKI therapy and treatment resistance.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.49 - The Impact of Baseline Systemic Inflammatory Status Parameters in Patients Treated with EGFR-Tyrosine Kinase Inhibitors (ID 2272)

      00:00 - 00:00  |  Author(s): Martin P Barr

      • Abstract
      • Slides

      Introduction

      Elevated neutrophil to lymphocyte ratio (NLR),derived neutrophil to lymphocyte ratio (dNLR),lung immune prognostic index (LIPI) and circulating tumour cells (CTCs) are associated with inferior outcomes in non-small cell lung cancer (NSCLC). The use of these parameters in patients treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is uncertain. We assessed the association of pre-treatment NLR, LIPI and CTCs on time to progression (TTP) and overall survival (OS) in patients treated with EGFR-TKIs.

      Methods

      Patients with existing EGFR-activating mutations on EGFR TKIs (cohort 1) and newly diagnosed, treatment naive (cohort 2) were recruited across three Irish Oncology centres over a two year period (n=21). Demographic characteristics were collected. Baseline NLR, dNLR (absolute neutrophil count/white blood cell concentration-absolute neutrophil count), LIPI (dNLR greater than 3 and LDH greater than ULN) consisted of 3 groups (good: 0 factors; intermediate: 1 factor; poor: 2 factors), and CTCs count was collected at baseline. CTCs were isolated from blood using ScreenCellÒ size exclusion technology.Cox proportional hazards analysis was used for overall survival (OS) and time to progression (TTP). Correlations were performed using the Wilcoxon sign rank test.

      Results

      16 (76%) of patients were female (median age 64.5), 20 (95%) were adenocarcinoma, 1 (5%) squamous cell carcinoma, 10 (48%) never smokers, 10(48%) ex-smokers.There was a significant correlation between LDH (p=0.02), CTCs (p=0.00067) and WCC in cohort 1. CTC count was also significantly correlated with LDH (p=0.001) in cohort 1. There was a significant correlation between LDH (p=0.003), NLR (p=0.0005) and WCC in cohort 2. NLR was also significantly associated with LDH (p<0.05). There was no significant correlation between dNLR and CTCs in either cohort. WCC, LDH, dNLR, CTCs and LIPI were not significantly associated with TTP and OS in either cohort.

      Conclusion

      Although there were positive correlations between baseline systemic inflammatory parameters, these were not prognostic for survival in patients treated with EGFR-TKI therapy. Larger clinical studies and sequential follow up parameter measurements during treatment will be valuable in assessing these markers during EGFR-TKI therapy.

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