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Y. Koh



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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-060 - Comparative Analysis of PD-L1 Expression between Circulating Tumor Cells and Tumor Tissues in Patients with Lung Cancer (ID 5402)

      14:30 - 14:30  |  Author(s): Y. Koh

      • Abstract

      Background:
      Blockade of programmed death receptor-1 (PD-1) pathway has been shown to be effective against solid tumors including lung cancer. Although PD-ligand 1 (PD-L1) expression on tumor tissue is expected as a potential predictive biomarker, its detection remains challenging due to its dynamic and unstable status. Here, we evaluated the PD-L1 expression on circulating tumor cells (CTCs) in patients with lung cancer and investigated its concordance with that on tumor tissues.

      Methods:
      CTCs were captured and immune-stained using microcavity array system. CTCs were defined as those positive for DAPI and cytokeratin (CK) and negative for CD45. PD-L1 expression on CTCs was evaluated by addition of the process of PD-L1 immunocytochemistry. For CTCs detection, 3 ml of peripheral whole blood was collected from the patients who consented in written form and PD-L1 immunohistochemistry was performed using corresponding tumor tissues.

      Results:
      Sixty-seven lung cancer patients were enrolled in the study between July 2015 and April 2016 at Wakayama Medical University. Patient characteristics were as follows: median age 71 (range, 39 to 86); male 72%; stage II-III/IV, 15/85%; non-small cell lung cancer (NSCLC)/small cell lung cancer (SCLC)/Other, 73/21/6%. CTCs were detected in 66 out of 67 patients (median 19; range, 0 to 115) and more than 5 CTCs were detected in 78% of patients. PD-L1 expressing CTCs were detected in 73% of patients and the proportion score (PS) of PD-L1 expressing CTCs ranged from 3% to 100%, suggesting intra-patient heterogeneity of PD-L1 expression on CTCs. Significantly more PD-L1 expressing CTCs were detected in patients without EGFR mutations than those with EGFR mutations (P = 0.0385). Tumor tissues were available from 27 patients and were immune-stained for PD-L1. No positive correlation was observed on PD-L1 expression between tumor tissues and CTCs based on PS (R[2 ]= 0.0103). Three adenocarcinoma cases with PD-L1-positive tumor tissue did not harbor any PD-L1 expressing CTCs and conversely, three adenocarcinoma cases with PD-L1-negative tumor tissue harbored PD-L1 expressing CTCs, showing the total discrepancy between tumor tissues and CTCs. It is also noteworthy that SCLC patients had perfect agreement on PD-L1 expression between tumor tissues and CTCs.

      Conclusion:
      PD-L1 expression was detectable on CTCs in lung cancer patients and intra-patient heterogeneity of its expression was observed. There was no agreement between tumor tissues and CTCs on PD-L1 expression though it may differ among tumor histologies. Further investigation is warranted to better understand the clinical significance of PD-L1 expressing CTCs.

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    P3.02b - Poster Session with Presenters Present (ID 494)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02b-073 - A Phase II, Liquid Biopsy Study Using Digital PCR in EGFR Mutated, Lung Cancer Patients Treated with Afatinib (WJOG 8114LTR) (ID 4754)

      14:30 - 14:30  |  Author(s): Y. Koh

      • Abstract

      Background:
      Liquid biopsy is an ideal strategy to monitor mutation status of cancer repeatedly and less invasively. In chronic myeloid leukemia, early remission of mutated cells was reported as a surrogate of longer efficacy. In epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC), to detect resistant mutation (exon20 T790M) during treatment is clinically important because newer tyrosine kinase inhibitors (TKIs) have been developed. Although some reports have mentioned the utility of liquid biopsy in EGFR mutated NSCLC, most were single-institutional, retrospective studies.

      Methods:
      West Japan Oncology Group (WJOG) 8114LTR is a multi-institutional, prospective liquid biopsy study in advanced NSCLC. Chemotherapy naïve, advanced NSCLC patients with EGFR-sensitizing mutation will receive afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Plasma DNA will be obtained from patients at baseline, 2, 4, 8, 12, 24, 48 weeks, and at PD. Three types of common EGFR mutations (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, pico-droplet digital PCR assay (RainDrop® system, RainDance Technologies, Billerica, MA). Primary endpoint of this study is the concordance of EGFR mutation status between tissue and plasma at baseline. Secondary endpoints are overall response rate, progression-free survival and safety. This is the first report on the primary endpoint and early remission rate based on mutated cf-DNA. This study was registered at UMIN (ID: 000015847).

      Results:
      Fifty-seven patients were registered and samples from 55 patients were analyzed. Clinical characteristics were as follows; median age: 69 years, male / female: 25/30, PS 0/1: 23/32, c-stage III / IV / post-operative relapse: 2/37/16, exon 19 deletion / exon 21 L858R: 28/27. Sensitivity of plasma sample was 63.6% among overall, while that was 84.6% in patients with distant metastasis. Eighty-two percent of plasma positive patients at baseline showed molecular response in plasma after two weeks of afatinib treatment. De novo T790M mutation was detected in one patient (2%) from plasma samples.

      Conclusion:
      Liquid biopsy seemed to be suitable especially in patients with distant metastasis. Early molecular remission (within two weeks) was observed in 70% of patients.