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K. Mohorcic



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    MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
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      MA08.09 - Monitoring Plasma EGFR Mutations during First Line Treatment with EGFR TKIs in NSCLC Patients (ID 4547)

      11:00 - 12:30  |  Author(s): K. Mohorcic

      • Abstract
      • Presentation
      • Slides

      Background:
      Genotyping cell free circulating DNA (cfDNA) is a non-invasive method of detecting EGFR mutations (EGFRmu) in plasma and may provide an option to identify patients who progress while treated with EGFR TKIs. The aim of our study was to monitor plasma EGFRmu and identify dynamic case specific changes in plasma EGFRmu during routine treatment of advanced EGFRmu NSCLC patients.

      Methods:
      Plasma was collected from patients with advanced EGFRmu NSCLC treated with first- or second-generation EGFR TKIs. Plasma EGFRmu were dynamically monitored consecutively at every scheduled visit. Cobas EGFR Mutation Test v1 and v2 (Roche, USA) was used to detect 42 mutations at EGFR gene in exons 18 to 21. Liquid biopsy progression (LBP) was determined as reappearance of EGFRmu in plasma after negativisation during treatment or increase of EGFRmu levels expressed by semi-quantitative index (SQI). Radiologic progression was determined in accordance with RECIST1.1 criteria.

      Results:
      From May 2014, 23 patients were treated with EGFR TKIs for advanced EGFRmu NSCLC; 20/23 had detectable activating mutations in plasma before any treatment and were therefore included in our analysis. Dynamic changes of plasma EGFRmu during 1[st] line EGFR TKI treatment are shown in Figure 1. Eight patients (40%) experienced RECIST 1.1 progression while on treatment, whereas one patient was inevaluable. In 4/8 patients (50%) LBP appeared at the same time as radiologic progression, in 3/8 patients (37%) LBP appeared before radiologic progression (8w, 14w, 20w before, respectively) and in 1 patient (12%) radiologic progression appeared 6w before LBP. Among patients who did not experience radiologic progression yet, some dynamic changes in cfDNA were also observed, but alterations in the SQI values were much smaller. Figure 1



      Conclusion:
      Monitoring EGFR mutations in plasma is a feasible and less invasive method in routine clinical practice and could be used as a predictive marker of progression on treatment with EGFR TKIs.

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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-008 - 2-Year Single Institution Experience with EGFR Plasma Testing in Advanced NSCLC (ID 4281)

      14:30 - 15:45  |  Author(s): K. Mohorcic

      • Abstract

      Background:
      Lung adenocarcinoma patients in advanced stage of disease that harbor EGFR sensitizing mutations are eligible for treatment with tyrosine kinase inhibitors (TKI) due to a high likelihood of response. Most patients will ultimately develop resistance at disease progression. The T790M mutation is a dominant resistance mechanism to TKI. EGFR plasma testing enables non-invasive monitoring and detection of T790M. We followed patients with EGFR sensitizing mutations by measuring EGFR mutations in plasma during TKI treatment.

      Methods:
      We analyzed patients who were diagnosed lung adenocarcinoma stage IV, detected EGFR sensitizing mutations in tumor tissue samples and treated with TKI at University Clinic Golnik. We collected baseline plasma samples prior to TKI treatment and consecutive plasma samples at different time intervals after initiation of therapy. At the beginning, two separate tests, cobasĀ® EGFR Mutation Test for tissue (CE-IVD) and plasma (under development) were used, and since October 2015 one test for tissue and plasma, cobasĀ® EGFR Mutation Test v2 (Roche, Pleasanton, CA, USA) is used. Detected EGFR mutations in plasma samples were expressed as semi-quantitative index (SQI) which reflects a proportion of mutated versus wild-type copies of the EGFR gene.

      Results:
      During 2-year period we collected 414 peripheral blood samples from 63 patients and performed 619 EGFR plasma tests. There are 25 patients with baseline and serial follow-up EGFR plasma tests, 16 patients with only serial follow-up EGFR tests since they started with TKI treatment before EGFR plasma testing was available, 5 patients are included in adjuvant setting, and 17 patients had no monitoring due to various reasons. Maximum number of EGFR plasma tests done per patient was 27 at 20 time-points. When introducing EGFR plasma testing, we prepared two aliquots of plasma out of 10 ml blood sample in EDTA-tubes and run test for both aliquots. Results of reproducibility study showed 95% concordance rate between both aliquots and thus we modified protocol to run the second aliquot only if the first one was negative. At disease progression, reappearance of EGFR sensitizing mutations with increasing SQI levels was detected. In 14 patients who progressed we detected T790M mutation, in 10 of them during monitoring TKI treatment. We also observed daily variation in EGFR mutation levels in the plasma.

      Conclusion:
      These data support the value of EGFR plasma testing to monitor the patient`s response to TKI and detect T790M resistance mutation prior to clinical progression in a routine clinical setting.