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K. Brosnan

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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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      P1.02-021 - Review of Clinical Outcomes Attributable to Next Generation Sequencing Based Broad Mutation Panel Testing in Lung Adenocarcinoma (ID 4701)

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

      • Abstract

      Molecular testing of lung cancer is currently performed on a relatively restricted set of standard-of-care markers (normally EGFR and ALK). The introduction of next generation sequencing (NGS) in clinical laboratories has permitted the adoption of broader testing using mutation panels. This study compared the number of mutations detected and outcomes generated as a result of replacing standalone EGFR and ALK assays with a combined mutation and gene fusion assay based on NGS in routine clinical practice.

      Panel testing was implemented using a bioinformatically selected subset of targets from the Thermo-Fisher Oncomine[TM] Focus assay. The results of testing were compared against the incumbent assay platforms (Roche Cobas® EGFR, Abbott Vysis[TM] ALK) to determine differences in mutation detection and resultant alterations to patient treatment.

      Over a 5 month period of testing, 231 lung adenocarcinomas were analysed using the extended mutation and fusion panel. In total 126 of 231 cases had a mutation or fusion identified; EGFR (n=33), KRAS (n=76), BRAF (n=8), ERBB2 (n=2), ALK-fusion (n=5), RET fusion (n=1). Additionally, one off-target fusion was detected during assay QC. Of the above results 31 EGFR and 5 ALK would have been detected using the benchmark Roche Cobas EGFR and Abbott Vysis ALK FISH methodologies. The additional detections can be classified as nonactionable (KRAS, BRAF) or actionable (RET fusion, 2 EGFR mutations not identified by Cobas, 2 ERBB2 mutations and one off-target fusion). Of the 6 actionable genetic lesions, 4 selected for targeted therapies in lung cancer (EGFR, ERBB2). Two fusions detected by this assay (CCDC6-RET and TMPRSS2-ERG) suggested an alternative diagnosis to that of lung cancer when reviewed with morphology, immunohistochemistry and clinicopathological correlation.

      When compared with standalone assay testing, panel testing of lung cancer identified mutations in an additional 39% of patients and identified genetic lesions that altered targeted therapy selection (2%) or diagnosis (1%). Broad mutation panel testing using NGS has shown itself to be superior at the level of clinical decision making by ascribing a molecular subtype to 39% more cancers and identifying an additional 2% of cases where targeted therapies may be of benefit. Crucially, the addition of 'off-target' mutations and fusions prompts re-examination and, where necessary, correction of primary diagnosis at a rate of 1% in our hands. This feature of panel testing has been overlooked and it is critical for the oncology and pathology communities to be aware of its significance.