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E. Thunnissen



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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.11-023 - Molecular Screening in Advanced Non-Small Cell Lung Cancer: A Systematic Review of Cost-Effectiveness Analyses for First-Line Therapy (ID 1931)

      09:30 - 09:30  |  Author(s): E. Thunnissen

      • Abstract

      Background
      Novel molecularly targeted therapies are increasingly licensed in conjunction with companion diagnostics to stratify patients with oncogenic aberrations and to help improve patients' likelihood of clinical benefit. Cost-effectiveness analyses (CEAs) are now expected to examine the value of molecular screening as well as traditional costs and benefits of therapeutic choices. The aim of this study was to assess the impact of first-line predictive biomarker screening on the cost-effectiveness of molecularly targeted agents in locally advanced or metastatic non-small cell lung cancer (NSCLC).

      Methods
      A systematic literature review was performed using MEDLINE, EMBASE and NHS EED. CEAs of epidermal growth factor receptor (EGFR)-, Kirsten RAS (KRAS)-, and anaplastic lymphoma kinase (ALK)-guided screening prior to first-line treatment were appraised according to a priori eligibility criteria. The impact of screening guided patient management was quantified by incremental cost-effectiveness ratios (ICERs) and expressed in 2013 US dollars. Sensitivity analyses were explored to examine the influence of extracted parameters on the ICERs. Methodological quality of the studies was assessed by standardized checklists.

      Results
      Based on the explicit test-treat combined strategy, eight CEAs met the inclusion criteria. Although six EGFR- and two ALK-guided diagnostic-therapeutic pairings were reviewed, none of the retrieved CEAs explored the potential benefits of KRAS mutation screening on the molecularly targeted agents in the front-line setting. Country-specific decisions regarding utilization of healthcare were conducted from the perspectives of the United States, England and Wales, France, Singapore and China. Efficacy data including biomarker prevalence (ALK: 1.6-4.4%, EGFR: 16.6-60%), sensitivity of the test (ALK: 67-100%, EGFR: 92-100%), specificity of the test (ALK: 93-100%, EGFR: 96-100%) and Quality-Adjusted Life Years (QALY) gained (ALK: 0.009-0.014, EGFR: 0.04-0.5) were extracted. Base-case costs for ALK- and EGFR-guided screening were $98-$1,421 and $105-$516, respectively. The ICERs of EGFR-guided test-treat strategy ranged from being less costly/more effective to unlikely to be cost-effective (ICER range: dominant-$160,123/QALY gained). The ICERs of ALK-guided strategy ranged from likely to be cost-effective to unlikely to be cost-effective (ICER range: $59,240-$213,869/QALY gained). Sensitivity analyses revealed that ICERs of molecularly enriched patient groups were profoundly dependent on the monthly costs of targeted agents (erlotinib, gefitinib, crizotinib) and duration of treatment. Conversely, at low biomarker frequencies, ICERs were influenced by the cost of the screening test. Test specificity, the proportion of advanced NSCLC patients correctly identified as not having EGFR/ALK positivity, was more influential than the test sensitivity. Although clinically imperative, re-biopsy and subsequent therapy were not explored. Furthermore, critical assessment of the CEAs revealed that justification of preferred methods, transparency of input parameters and generalizability of results affected quality.

      Conclusion
      This study investigates indications of cost-effective screening of 'actionable' molecular aberrations and highlights the impact of clinical and cost parameters on the ICERs. While advancements in mechanisms of resistance and histological transformations will shed light on the future of lung cancer care, CEAs of novel diagnostic-therapeutic pairings will continue to help informed decision-making of all stakeholders.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-046 - EML4-ALK monitoring of crizotinib response in blood platelets and plasma of NSCLC patients (ID 3267)

      09:30 - 09:30  |  Author(s): E. Thunnissen

      • Abstract

      Background
      The discovery of various genetic alterations that underlie lung cancer has opened-up a new era in the development of specifically targeted therapies employing specific alteration-dependent inhibitors. In the vast majority of NSCLC patients genetic alterations occur in EGFR (20-25%), BRAF (3%), and ALK (3-10%), seemingly in a predominant mutual exclusive manner. Hence, patient stratification for EGFR, KRAS, BRAF, and ALK alterations is becoming common practice among oncologists. The mutational status of NSCLC patients is considered dynamic and can change in due course of the disease and selection in response to therapy. Longitudinal monitoring of the mutational status of NSCLC patients is of crucial importance to tailor targeted therapy by adapting treatment regimens according to mutational status. However, technical challenges associated with serial tumor biopsy constitute a major challenge in longitudinal molecular monitoring and targeted treatment of NSCLC patients. Blood-based assays may overcome such limitations and allow for frequent assessment of the mutational status.

      Methods
      Here, tumor tissue, platelets, and/or plasma of NSCLC patients were collected and analyzed for the presence of translocated ALK using FISH, IHC, and/or RT-PCR. Monitoring of EML4-ALK in platelets and plasma was performed by RT-PCR on EML4-ALK positive patients treated with crizotinib and correlated to the clinical response as measured by serial radiographic CT.

      Results
      From a multicenter cohort of NSCLC patients we identified EML4-ALK positive patients by FISH, IHC, and RT-PCR, for blood platelet and/or plasma isolation. In blood platelets of ALK positive NSCLC patients (n=24) and ALK negative control subjects (n=54) we demonstrated an EML4-ALK test sensitivity of 70-80% and specificity of 100%. We detected EML4-ALK in plasma of ALK positive NSCLC patients (n=22), however with inferior sensitivity of 20-30%. In addition, longitudinal EML4-ALK monitoring in blood platelets of an ALK positive NSCLC patient correlated with the crizotinib response.

      Conclusion
      We demonstrate here that blood platelets of NSCLC patients are a biosource for the detection of the EML4-ALK translocation and may proof useful for longitudinal monitoring of ALK inhibitors in NSCLC patients, with superior outcome over plasma.