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Izidor Kern



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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-14 - Monitoring of EGFR Mutations During Osimertinib Treatment in Advance EGFR-Mutant T790M Positive NSCLC (Now Available) (ID 1469)

      09:45 - 18:00  |  Author(s): Izidor Kern

      • Abstract
      • Slides

      Background

      Genotyping cell free circulating DNA (cfDNA) is a non-invasive method of detecting EGFR mutations (EGFRmu). The aim of our study was to investigate whether changes in the levels of plasma EGFRmu are associated with clinical outcomes of advanced T790M positive EGFRmu patients treated with osimertinib.

      Method

      Single centre prospective observational study was performed with plasma being collected from patients with advanced EGFRmu T790M positive NSCLC routinely treated with second line osimertinib. Dynamical monitoring of cfDNA was performed at every scheduled visit (8 weeks) until disease progression. Cobas EGFR Mutation Test v1 and v2 (Roche, USA) was used to detect 42 mutations at EGFR gene in exons 18 to 21, including T790M mutation. Radiological assessment was performed in accordance with RECIST 1.1 criteria.

      Result

      Twenty-seven patients were treated with osimertinib from October 2015 until December 2018. At the beginning of osimertinib treatment only 17/27 (63%) patients had detectable T790M mutation in plasma, but almost all patients 26/27 (96%) had detectable plasma EGFR activating mutations (AM). During osimertinib treatment T790M mutation was cleared from plasma in all 17 patients regardless of response to treatment. On the contrary, only 12/26 (45%) patients had AM plasma clearance. Only 3 of them had had progress at median follow up of 17.5 months, what demonstrates significantly longer progression-free survival (PFS) of patients with AM plasma clearance compared to patients without AM clearance (HR 0.19; 95% CI 0.05 – 0.70, p = 0.01) (Figure 1). Of the 14 patients that progressed during the observation period all had AM reapperance in cfDNA at the time on progression, while T790M only recurred in one.

      mohorcic_wclc_picture_figure.jpg

      Conclusion

      Clearance of EGFR AM in plasma during osimertinib treatment is associated with longer PFS, while clearance of T790M has no impact on survival in our small group of patients. Dynamic changes in EGFR AM might be a useful marker of outcome in patients treated with osimertinib, but further studies are needed.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-30 - PD-L1 Testing and Clinical Benefit in Patients Treated with CPI (Now Available) (ID 1672)

      10:15 - 18:15  |  Author(s): Izidor Kern

      • Abstract
      • Slides

      Background

      PD-L1 expression in tumor cells should predict better response rate in lung carcinoma patients treated with immune checkpoint inhibitors.

      Method

      Retrospective analysis of 46 NSCLC lung cancer patients with cytology/pathology samples from primary tumor/metastasis tested for PD-L1 expression and comparing the PD-L1 testing results with clinical benefit. Follow-up period was 6 to 24 months. Samples were stained with PD-L1 mouse monoclonal antibody (clone 22C3, DAKO, Denmark) or with rabbit monoclonal antibody (clone SP263, Ventana/Roche, USA) on an automated staining platform (Benchmark ultra, Ventana/Roche, USA). Samples were divided into four categories: Cytology, histology, primary tumor and metastasis. Number of positive tumor cells was assessed semiquantitatively and divided into three categories: 0%, 1 to 49% and 50 to 100%. We compared PD-L1 expression with clinical course of patients treated with immune checkpoint inhibitors (nivolumab, pembrolizumab and atezolizumab), considering complete response, partial response and stable disease (RECIST criteria) as clinical benefit. Progress of the disease was considered as no clinical benefit.

      Result

      We had 37% cytological and 63% histological samples. Overall PD-L1 expression was present in 76% of all samples (1 to 49% and 50 to 100% categories, 13% and 63%, respectfully). We observed clinical benefit in 33 patients (5, 5 and 23 with 0%, 1 to 49% and 50 to 100%, respectively). Progress of the disease was observed in 13 patients (6, 1 and 6 with 0%, 1 to 49% and 50 to 100%, respectively). Out of 29 patients with histological samples, 22 had clinical benefit (2, 5 and 15 with 0%, 1 to 49% and 50 to 100%, respectively). Progress of the disease was observed in 7 patients (5, 0 and 2 with 0%, 1 to 49% and 50 to 100%, respectively). Out of 17 patients with cytological samples 11 had clinical benefit (3, 0 and 8 with 0%, 1 to 49% and 50 to 100%, respectively). Progress of the disease was observed in 6 patients (1, 1 and 4 with 0%, 1 to 49% and 50 to 100%, respectively). We had 29 samples from primary tumor and 17 samples from metastasis. 23 patients with primary tumor sample (2, 4 and 16 with 0%, 1 to 49% and 50 to 100%, respectively) and 10 with metastasis sample (3, 0 and 7 with 0%, 1 to 49% and 50 to 100%, respectively) had clinical benefit. Progress of the disease was observed in 6 patients with primary tumor sample (4, 0 and 2 with 0%, 1 to 49% and 50 to 100%, respectively) and in 7 patients with metastasis sample (2, 1 and 4 with 0%, 1 to 49% and 50 to 100%, respectively) .

      Conclusion

      Histological samples from primary tumors seem to have the best, while cytological samples from metastases the poorest predictive value for assessment of clinical benefit for NSCLC patients treated with immunotherapy.

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