Author of

• 34715

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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

  • 34726

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    P34.07 - Quantification of BIM mRNA In Circulating Tumor Cells Of Osimertinib-treated Patients with EGFR Mutation-positive Lung Cancer (ID 1490)

    00:00 - 00:00  |  Presenting Author(s): Kazutoshi Isobe
    • Abstract
    • Slides

    Introduction
    

    Osimertinib has a high response rate in untreated epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) patients. However, currently there are no biomarkers to determine the efficacy of osimertinib. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicted a poor prognosis of osimertinib treatment in patients with EGFR mutation-positive NSCLC.

    Methods
    

    Patient selection criteria included EGFR-tyrosine kinase inhibitor untreated NSCLC patients with advanced stage or postoperative recurrence with EGFR sensitive mutations (exon19 deletion or L858R mutation). Informed consent was obtained from the participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline, during osimertinib administration, at 2 and 4 months, and then every 4 months thereafter. CTCs were collected using the ClearCell^® FX system. Quantitative real-time PCR was performed. To correct for differences in quality and quantity between samples, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference gene. The targets were obtained from the same mRNA preparations. The relative expression of BIM-γ in mRNA from CTCs, normalized to GAPDH, was calculated using the KCL22 cell line for calibration.

    Results
    

    We enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib between April 2018 and December 2019. Patient characteristics included 13 males and 17 females with a median age of 70 years (range 68–85), performance status 0 in 20 patients, performance status 1 in 8 patients, and performance status 2 in 2 patients. Pathological classifications of lung cancer were adenocarcinoma in 28 patients and squamous cell carcinoma in 2 patients. Clinical stage IIIB was observed in 2 patients, stage IV in 22 patients and recurrence after surgical resection occurred in 8 patients with distant metastases. Thirty cases had an EGFR mutation in the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. The median counts of CTCs at baseline were 9 (range 0–124)/10 mL, and the median BIM-γ mRNA expression was 0.073 (range 0–1.37). There was no significant correlation between the CTCs counts and BIM-γ mRNA expression in CTCs. In addition, the response rate of osimertinib was poor in the BIM-γ mRNA high expression group(n=15) compared with the BIM-γ mRNA low expression group (n=15) (26% vs 73.3% p=0.011). Progression-free survival of osimertinib between groups was not significantly different (p=0.21).

    Conclusion
    

    Overexpression of BIM-γ mRNA in CTCs of EGFR mutation-positive NSCLC patients can be a biomarker of poor responsiveness of osimertinib.

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