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R. Freedman



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    ORAL 06 - Next Generation Sequencing and Testing Implications (ID 90)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      ORAL06.06 - Impact of Reflex EGFR/ALK Testing on Time-To-Treatment and Integration of Personalized Medicine in Advanced Non-Small Cell Lung Cancer Patients (ID 2290)

      11:59 - 12:10  |  Author(s): R. Freedman

      • Abstract
      • Presentation
      • Slides

      Background:
      Testing for biomarkers including EGFR mutations and ALK rearrangements is standard of care in the management of advanced non-small cell lung cancer (NSCLC), as it determines optimal systemic therapy (ST). Our centre began EGFR testing March 2010 and ALK April 2012. Initially, EGFR/ALK were requested by medical oncologists (MO) when patients were deemed eligible for EGFR or ALK targeted therapy. To expedite biomarker information to MO for rapid initiation of ST in patients with advanced stage or earlier stage disease that developed recurrence, June 2013 we implemented a multidisciplinary approach termed “reflex testing”. This was defined as our pathologists requesting EGFR/ALK at time of diagnosis of non-squamous NSCLC irrespective of a patient’s clinical stage. If tissue was at an outside centre, clerical staff requested EGFR/ALK at time of referral to MO. The objective of this study was to determine if reflex testing improved time-to-treatment (TTT) and the integration of personalized medicine in patients with advanced NSCLC.

      Methods:
      This was a retrospective chart review of patients with non-squamous NSCLC seen by MO at the Sunnybrook Odette Cancer Centre from March 18, 2010 to April 30, 2014. Patient and EGFR/ALK test characteristics were compared before and after reflex testing was implemented using Chi-square tests of association. Time outcomes were compared using Mann-Whitney U non-parametric tests. TTT was defined as the interval between first MO visit with advanced NSCLC to initiation of ST.

      Results:
      Of the 301 patients included, median age was 68, 43% female, 65% Caucasian, 75% smokers, 93% adenocarcinoma, 22% EGFR positive and 1% ALK positive. The majority presented with stage IV (65%) and 82% either presented with or developed advanced NSCLC. In advanced NSCLC patients (n=247), reflex testing significantly reduced median TTT compared to routine testing [(24 days (IQR: 7 to 42) vs. 36 days (IQR: 16 to 72), p=0.04)], reduced the rate of EGFR unknown (4% vs. 26%, p=0.002) and ALK unknown (10% vs. 50%, p<0.001). There was minimal impact on advanced NSCLC patients receiving any first-line ST (58% vs. 63%, p=0.48). However, among these patients, with reflex testing, fewer were initiated on first-line ST without biomarker results known by MO (EGFR 23% vs. 39%, p=0.12, ALK 17% vs. 42%, p=0.02), and at last follow up significantly fewer had EGFR unknown (0% vs. 13%, p=0.004) and ALK unknown (7% vs. 38%, p=0.003). Across all stages, rates of EGFR results available to MO at first consultation increased (34% vs. 4%, p<0.001). Reflex testing also impacted the quality of biomarker testing with a decrease in unsuccessful EGFR tests due to inconclusive results, insufficient or inappropriate tissue, or tissue not sent from holding lab to testing lab (4% vs. 15%, p=0.03).

      Conclusion:
      A multidisciplinary approach to earlier biomarker testing in NSCLC is feasible. Reflex testing for EGFR/ALK improved TTT and the integration of personalized medicine for patients with advanced NSCLC by improving biomarker testing rates, the quality of testing and fewer patients given ST without biomarkers known. These outcomes provide support for reflex EGFR/ALK testing by pathologists at time of diagnosis of non-squamous NSCLC.

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