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M. Schuler

Moderator of

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    ISS08 - A prIME Oncology Satellite Symposium Supported by Boehringer Ingelheim Pharma GmbH & Co. KG.: Reaching New Heights in the Management of Non-Small Cell Lung Cancer: Focus in EGFR-Targeted Therapy (ID 441)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 7
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      ISS08.01 - Welcome & Warm-up Quiz (ID 7146)

      17:45 - 17:50  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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      ISS08.02 - Key Decision Points for Personalized Patient Care of Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 7147)

      17:50 - 18:00  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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      ISS08.03 - Managing EGFR–Mutant Adenocarcinoma: What is the Optimal First-Line Approach? (ID 7148)

      18:00 - 18:20  |  Author(s): B. Melosky

      • Abstract

      Abstract not provided

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      ISS08.04 - Tackling Acquired Resistance to EGFR– Targeted Therapy: Evaluating Current and Emerging Treatment Strategies (ID 7149)

      18:20 - 18:30  |  Author(s): K. Park

      • Abstract

      Abstract not provided

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      ISS08.05 - Contemporary Management of Squamous Cell Carcinoma: What is the Role of EGFR–Targeted Therapy in the Era of Immunotherapy? (ID 7150)

      18:30 - 18:45  |  Author(s): M. Nicolson

      • Abstract

      Abstract not provided

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      ISS08.06 - Quiz Questions Revisited and Questions from the Audience (ID 7151)

      18:45 - 19:00  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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      ISS08.07 - prIME Points™ (ID 7152)

      19:00 - 19:05  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided



Author of

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    ISS08 - A prIME Oncology Satellite Symposium Supported by Boehringer Ingelheim Pharma GmbH & Co. KG.: Reaching New Heights in the Management of Non-Small Cell Lung Cancer: Focus in EGFR-Targeted Therapy (ID 441)

    • Event: WCLC 2016
    • Type: Industry Supported Symposium
    • Track:
    • Presentations: 4
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      ISS08.01 - Welcome & Warm-up Quiz (ID 7146)

      17:45 - 17:50  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

    • +

      ISS08.02 - Key Decision Points for Personalized Patient Care of Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 7147)

      17:50 - 18:00  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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      ISS08.06 - Quiz Questions Revisited and Questions from the Audience (ID 7151)

      18:45 - 19:00  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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      ISS08.07 - prIME Points™ (ID 7152)

      19:00 - 19:05  |  Author(s): M. Schuler

      • Abstract

      Abstract not provided

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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-025 - Rapid and Highly Sensitive EGFRdelEx19 and KRAS Exon 2 Mutation Detection in EBUS-TBNA Specimen of Lung Adenocarcinoma (ID 4000)

      14:30 - 14:30  |  Author(s): M. Schuler

      • Abstract

      Background:
      First-line treatment with afatinib prolongs overall survival in patients with metastatic non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion mutations. Conversely, somatic KRAS mutations are negative predictors for benefit from EGFR-targeting agents. Rapid availability of these biomarker results is mandatory to prevent delayed or inferior treatments. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well-established for lung cancer diagnosis and staging. Next generation sequencing (NGS) via targeted resequencing allows simultaneous interrogation for multiple mutations, but has its limitations based on the amount of tumor tissue required and assay times. RT-PCR using Light-Cycler technology (LC-RTPCR) is a rapid and sensitive assay to detect somatic mutations in various tissues from NSCLC patients. The study’s aim was to analyze if LC-RTPCR is feasible for rapid EGFRdelEx19 and KRAS Exon 2 mutation detection in EBUS-TBNA samples and to compare results with results obtained via standard NGS mutation analyses.

      Methods:
      48 surplus EBUS-TBNA samples (38 lymph nodes, 10 primary tumor) from 47 patients with pulmonary adenocarcinoma were analyzed. Two samples were collected per lymph node. One was used for routine cytology, the other was freshly frozen (ff). DNA from ff-biopsies was extracted using Genomic DNA buffer set (QIAgen, Germany). Mutation analysis by LC-RTPCR was conducted as previously described. NGS was performed on MiSeq (Illumina) via targeted resequencing using a customized multiplex-PCR panel covering 36 exons from 11 genes. Mutations were annotated with a minimum frequency of 2%. Processing time was approximately 4 days for NGS and 2 hours for LC-RTPCR analyses.

      Results:
      NGS of EBUS-TBNA samples was technically feasible for both markers in 22 (46%) samples, for EGFR testing in 32 (67%) samples, and for KRAS in 23 (48%) samples. EGFRdelEx19 mutations were detected in four (8.3% of intention-to-screen), and KRAS Exon 2 mutations in 15 cases (31%) cases. LC-RTPCR was technically feasible in all cases. All mutations detected by NGS were also detected by LC-RTPCR. LC-RTPCR detected three additional KRAS Exon 2 mutations and three additional EGFRdelEx19 mutations. NGS detected additional mutations in 4 cases (2 EGFR Exon 21, 1 KRAS Codon 61, 1 PIK3CA).

      Conclusion:
      LC-RTPCR is a rapid, highly sensitive method to detect mutations of immediate therapeutic relevance, such as EGFRdelEx19 and KRAS Exon 2 mutations, in limited EBUS-TBNA specimens from metastatic NSCLC patients. It is of value as rapid and sensitive initial assay in a two-step diagnostic process for first-line treatment decision, incorporating broader biomarker panels as second step.

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    SC04 - EGFR Tyrosine Kinase Inhibitors: A Model for Successful Drug Development (ID 328)

    • Event: WCLC 2016
    • Type: Science Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      SC04.04 - Liquid Biopsies for Dynamic Monitoring of EGFR Mutations in Lung Cancer (ID 6616)

      12:00 - 12:20  |  Author(s): M. Schuler

      • Abstract
      • Slides

      Abstract:
      Somatic mutations clustering in exons 18 to 21 of the EGFR gene characterize distinct lung cancer biologies. Patients with metastatic EGFR-mutated lung cancer are exquisitely sensitive to targeted agents inhibiting the EGFR tyrosine kinase, which have demonstrated superior progress-free survival and, in some instances, overall survival when compared to platinum-based chemotherapy in first-line treatment. Several studies have shown that EGFR mutations can be detected by highly sensitive assay technology in free DNA circulating in the blood from patients with EGFR-mutated lung cancers 1,2,3. Circulating EGFR-mutated DNA may drop below the level of detection in patients responding to EGFR-TKI, and persistence or reoccurrence of circulating EGFR-mutated DNA may associate with primary and acquired resistance 1,3. In addition, clonal evolution of EGFR-mutated lung cancers under EGFR-TKI therapy can be mirrored by the detection of gatekeeper mutations, such as EGFR T790M or the EGFR C797S, in circulating DNA 4,5. Hence, mutation analysis in circulating free DNA has been suggested as a clinically more feasible and less invasive method for detection of predictive genomic biomarkers and treatment monitoring in advanced lung cancer. The development of more sensitive technologies and bioinformatic algorithms enables the study of comprehensive genomic biomarker panels in blood-derived DNA, which cover a broader spectrum of actionable mutations in treatment-naïve patients and those with acquired TKI resistance. Currently, there are still several limitations to overcome. First, the predictive value of a mutation detected in blood-derived DNA cannot be simply extrapolated from validation studies conducted with tumor-derived DNA. In consequence, prospective clinical validation of blood-based biomarkers is mandatory. Secondly, most studies comparing EGFR mutation detection in tumor and “liquid” biopsies side-by-side reveal inferior sensitivity of blood-based assays. Also, there is a considerable degree of discordance between such assays 4,6,7. Thus, “negative” findings in circulating tumor DNA have to be confirmed by a second assay in tumor-derived DNA. Apart from inflating spending on molecular diagnostics, this may result in further treatment delays, which is hard to bear for patients in particular in the first-line setting. While these obstacles may be soon overcome by technological advances and evolving data from validation studies, “liquid biopsies” focusing on DNA and/or RNA will always miss out on the histopathological information that can be derived from a biopsy of a tumor or metastasis. In the era of immunomodulatory antibody therapy information of tumor-infiltrating immune and stromal cells as well as expression of biomarkers by specific cell populations or with spatial variation become increasingly important. Until this information cannot be reproducibly derived by novel assay technologies the detection of genomic biomarkers in blood-derived DNA will become a highly valuable, additive modality for specific scenarios of primary diagnosis and treatment monitoring. References: 1 N Engl J Med. 2008 Jul 24;359(4):366-77. 2 Clin Cancer Res. 2009 Apr 15;15(8):2630-6. 3 PLoS One. 2014 Jan 21;9(1):e85350. 4 Lung Cancer. 2015 Dec;90(3):509-15. 5 Nat Med. 2015 Jun;21(6):560-2. 6 Clin Cancer Res. 2016 Mar 1;22(5):1103-10. 7 J Clin Oncol. 2016 Jun 27. pii: JCO667162.

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.