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C.A. Uyl-De Groot



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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-014 - PET-based radiotherapy planning is highly cost-effective compared to CT-based planning: a model-based evaluation. (ID 1608)

      09:30 - 16:30  |  Author(s): C.A. Uyl-De Groot

      • Abstract

      Methods
      The cost-effectiveness analysis was performed using a previously developed decision model that simulates the disease progression of individual lung cancer patients until they are deceased or have reached a pre-specified time-horizon of 3 years. Simulated patients move from the start of radiotherapy treatment to the absorbing state of death, potentially visiting the intermediate health states ‘local recurrence’ and ‘metastasis’. Transition rates in the model were estimated by multi-state statistical modelling and include the impact of patient and tumour features on disease progression. Data for model quantification was available for 200 NSCLC patients with inoperable stage I-IIIB, provided by the Maastro Clinic. Resource use estimates, costs and utilities were obtained from the data of the Maastro Clinic, the literature and Dutch guidelines. Primary outcomes were the difference in life years, quality adjusted life years and costs and the incremental cost-effectiveness and cost-utility ratio (ICER and ICUR) of PET-CT versus CT based radiotherapy planning. Model outcomes were obtained from averaging the outcome for 50 000 simulated patients. A probabilistic sensitivity analysis was done as well as a number of scenario analyses.

      Results
      The incremental costs of PET-CT based planning were €581 (95% CI: €-4474 – €6064) for 0,42 incremental life years (95% CI: 0,20 – 0,62) and 0,33 quality adjusted life years gained (95% CI: 0,16 – 0,54) (figure 1). The base-case scenario resulted in an ICER of €1370 per life year gained and an ICUR of €1761 per quality adjusted life year gained. The probabilistic analysis gave a 35% probability that PET-CT based planning improves health outcomes at reduced costs and a 65% probability that PET-CT based planning is more effective at slightly higher costs.Figure 1 Figure 1. Results of probabilistic sensitivity analyses showing incremental costs and incremental life years for PET-CT-based radiotherapy treatment planning compared to CT-based radiotherapy treatment planning.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P1.11-022 - Retrospective Longitudinal Chart Review of Patients with Advanced Non-Small Cell Lung Cancer in the Netherlands: A Quantification of Disease Burden (ID 1855)

      09:30 - 16:30  |  Author(s): C.A. Uyl-De Groot

      • Abstract

      Background
      The availability of novel therapeutic regimens has led to increase in duration of treatment and utilization of healthcare in non-small cell lung cancer (NSCLC). Although medical resource use and costs were assessed in previous studies, characterization of disease burden exclusively for advanced-stage, in real-world setting is scarce. The aims of our study were to quantify medical costs of stage IIIB/IV NSCLC and identify components of care, that are likely to alter in light of new developments, in Dutch clinical practice.

      Methods
      A retrospective longitudinal chart review was performed to obtain healthcare utilization of patients, age ≥18 years, with stage IIIB/IV NSCLC (based on the sixth edition of tumor-node-metastasis classification) who received first- and subsequent-line of systemic anti-cancer therapy (SACT). As part of the LUng Cancer Economics and Outcomes Research (LUCEOR), a multi-country retrospective patient chart review, two academic and two non-academic Dutch hospitals participated in the study. Patients who deceased before April 2010 were included. The components of care, from the initiation of first-line SACT until death, were quantified by twelve distinct categories. Total and monthly medical costs attributable to each component were calculated and expressed in 2012 US dollars. Outcomes were fit with statistical models to compare trends. Potential predictors of lifetime NSCLC costs and variability were examined.

      Results
      A total of 134 patients, 65% (87/134) males, of age 63 ± 9.7 (mean ± SD) years were included. While 34% (46/134) of patients were presented with adenocarcinoma, the proportion of large-cell carcinoma, squamous cell carcinoma and NSCLC not otherwise specified were 33% (44/134), 29% (39/134) and 4% (5/134), respectively. The clinical stage at the start of first-line SACT were 28% (37/134) IIIB and 72% (97/134) IV. Aside from the relatively small subset of patients (12%, 16/134) harboring oncogenic drivers, platinum-based combination chemotherapy regimens were the mainstay of treatment. For a median survival of 7.1 months (95% CI 5.9-8.1), total lifetime costs were averaged to $39,992 ± $20,928 per patient. The influential cost-drivers across all lines of therapy were hospitalizations ($15,521± $16,511) and SACT ($11,628± $7,583), mainly platinum-based gemcitabine or docetaxel. Monthly costs per patient were amounted to $11,932± $14,571. The degree of associations between predictors and outcomes were observed for clinical stage of disease at the start of SACT, administration of prior treatment and smoking history. Although clinically imperative, age and gender were not predictors of variability of healthcare costs at alpha ≤0.05.

      Conclusion
      Real-world medical costs, in particular hospital admissions and SACT, are substantial in the management of stage IIIB/IV NSCLC in the Netherlands. In a molecularly enriched patient population, biomarker-driven treatments are expected to result in higher likelihood of clinical benefit. Consequently, the average hospitalization costs and long-term management of treatment-related events are likely to reduce. Future research assessing the quantification of disease burden based solely on molecularly targeted agents in daily practice is encouraged. These results may collectively inform decision-making of registration, reimbursement and pricing of interventions in NSCLC.

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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 - 16:30  |  Author(s): C.A. Uyl-De Groot

      • 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.