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A Systematic Review of the Cost-Effectiveness Analyses of Anaplastic Lymphoma Kinase (ALK) Inhibitors in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

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Abstract

Background

The anaplastic lymphoma kinase (ALK) inhibitor treatment landscape is rapidly evolving, providing patients with ALK-positive (+) non-small cell lung cancer (NSCLC) with multiple therapy options, multiple lines of treatments, and prolonged survival. However, these recent treatment advances have resulted in additional increases in treatment costs. The objective of this article is to review the economic evidence of ALK inhibitors in patients with ALK+ NSCLC.

Methods

The systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) systematic reviews of economic evaluation. The population included adult patients with locally advanced (stage IIIb/c) or metastatic (stage IV) NSCLC cancer with confirmed ALK fusions. The interventions included the ALK inhibitors alectinib, brigatinib, ceritinib, crizotinib, ensartinib, or lorlatinib. The comparators included the listed ALK inhibitors, chemotherapy, or best supportive care. The review considered cost-effectiveness analysis studies (CEAs) that reported incremental cost-effectiveness ratio in quality-adjusted life years and/or in life years gained. Published literature was searched in Medline (via Ovid) by 4 January 2023, in Embase (via Ovid) by 4 January 2023, in International Pharmaceutical Abstracts (via Ovid) by 4 January 2023, and in Cochrane library (via Wiley) by 11 January 2023. Preliminary screening of titles and abstracts was conducted against the inclusion criteria by two independent researchers followed by a full text of selected citations. Search results are presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Critical appraisal was conducted using the validated Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) tool as well as the Phillips et al. 2004 appraisal tool to assess the reporting and quality of the economic evaluations. Data were extracted from the final set of articles and presented in a table of characteristics of included studies, an overview of study methods of included studies, and a summarization of outcomes of included studies.

Results

A total of 19 studies met all inclusion criteria. The majority of the studies were in the first-line treatment setting (n = 15). Included CEAs varied in the interventions and comparators being evaluated and were conducted from different country perspectives, limiting their comparability. Outcomes from the included CEAs showed that ALK inhibitors may be considered a cost-effective treatment option for patients with ALK+ NSCLC in the first-line and subsequent lines of treatment setting. However, the probability of cost effectiveness of ALK inhibitors ranged from 46 to 100% and were mostly achieved at willingness-to-pay thresholds of $100,000 USD or higher (> $30,000 or higher in China) in the first-line treatment setting and at thresholds of $50,000 USD or higher in subsequent lines of treatment setting. The number of published full-text CEAs is low and the studies represent a handful of country perspectives. The source of survival data was dependent on data from randomized controlled trials (RCTs). Where RCT data were not available, indirect treatment comparisons or matched adjusted indirect comparisons were performed using efficacy data from different clinical studies. Real world evidence was rarely used for efficacy and costing data inputs.

Conclusion

The findings summarized available evidence on cost effectiveness of ALK inhibitors for the treatment of patients with locally advanced or metastatic ALK+ NSCLC across lines of treatment settings and generated a valuable overview of analytical approaches utilized to support future economic analyses. To help further inform treatment and policy decisions, this review emphasizes the need for comparative cost effectiveness of multiple ALK inhibitors simultaneously using real-world data sources with broad representation of settings.

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Acknowledgements

The authors would like to thank the liaison and education librarian Ms. Glyneva Bradley-Ridout at the University of Toronto for her help and contribution to the study.

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Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

    Lara Chayab, Natalia Konstantelos & Mina Tadrous

  2. School of Pharmacy, University of Waterloo, Waterloo, ON, Canada

    William W. L. Wong

  3. Princess Margaret Hospital, Toronto, ON, Canada

    Natasha B. Leighl

  4. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Natasha B. Leighl

  5. Women’s College Research Institute, Toronto, ON, Canada

    Mina Tadrous

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  1. Lara Chayab
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  2. Natalia Konstantelos
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  5. William W. L. Wong
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Correspondence to Lara Chayab.

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Conflicts of interest

LC is an employee of Hoffmann La-Roche, a pharmaceutical and diagnostics company. This systematic review is being conducted independent of LC’s place of employment. MT received consulting fees from CADTH and Green Shield Canada. NBL has received institutional grant funding from Amgen, Array, AstraZeneca, Bayer, BMS, Eli Lilly, EMD Serono, Guardant Health, Inivata, MSD, Novartis, Pfizer, Roche, and Takeda as well as honoraria for independent CME lectures from Amgen, BMS, EMD Serono, MSD, Novartis, Sanofi Genzyme, and Takeda.

Author contributions

Author 1: Lara Chayab: Conceived and designed the systematic review protocol (objective, research question, PICO, inclusion/exclusion criteria, and methodology); Conducted the systematic review including the search strategy, study selection, assessment of methodological quality, data extraction, analysis, synthesis, and presentation; Drafted the manuscript and revised manuscript on the basis of editor and reviewer comments; Approver of the final manuscript version to be published; Accountable to all aspects of the systematic review conduct and reporting. Author 2: Natalia Konstantelos: Provided substantial intellectual contribution to the systematic review methodology design and conduct; Conducted the systematic review alongside author 1 in the capacity of independent reviewer, including study selection, assessment of methodological quality, and data extraction; Provided critical revisions to the results section of the manuscript including data analysis and presentation as well as to the full manuscript, ensuring overall accuracy, consistency, and rigor; Assisted in addressing reviewer comments and helped revise manuscript prior to resubmission; Approver of the final manuscript version to be published; Accountable to all aspects of the systematic review conduct and reporting. Author 3: Natasha B. Leighl: Provided substantial intellectual contribution to the conception and design of the systematic review objective, research question, PICO, and inclusion/exclusion criteria from a clinical (medical oncologist) expert perspective; Provided critical revisions to the background, result interpretation, discussion, and relevance/conclusion of the manuscript; Assisted in addressing reviewer comments and provided input to revised manuscript prior to resubmission; Approver of the final manuscript version to be published; Accountable to all aspects of the systematic review conduct and reporting. Author 4: Mina Tadrous: Provided substantial intellectual contribution to the conception and design of the systematic review protocol (objective, research question, PICO, inclusion/exclusion criteria, and methodology) from a health services and outcomes research expert perspective; Provided critical revisions to the results’ presentation and interpretation, to the discussion, and to the conclusion sections of the manuscript, as well as to the full manuscript, ensuring overall accuracy, consistency, and rigor; Assisted in addressing reviewer comments and provided input to revised manuscript prior to resubmission; Approver of the final manuscript version to be published; Accountable to all aspects of the systematic review conduct and reporting. Author 5: In supervision, William W.L. Wong: Provided co-leadership (and oversight to) the conception and design of the systematic review protocol and study conduct together with author 1; Conducted the systematic review alongside author 1 and author 2 in the capacity of third reviewer, which required oversight of the study selection, assessment of methodological quality, and data extraction processes; Provided critical and intellectual revisions to the full manuscript, ensuring relevance, rigor, and integrity throughout with special focus on the abstract, methodology description, the results’ analysis, presentation, and interpretation, and the key points for decision makers; Assisted in addressing reviewer comments and helped revise manuscript prior to resubmission; Approver of the final manuscript version to be published; Accountable to all aspects of the systematic review conduct and reporting.

Funding

The team received no external funding for this study.

Data availability

The systematic review protocol is available in the International Prospective Register of systematic review, PROSPERO, under registration code CRD42022308680; https://www.crd.york.ac.uk/prospero/. Results of the search strategy are included in this published article (and its supplementary information files).

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Chayab, L., Konstantelos, N., Leighl, N.B. et al. A Systematic Review of the Cost-Effectiveness Analyses of Anaplastic Lymphoma Kinase (ALK) Inhibitors in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC). PharmacoEconomics 41, 945–980 (2023). https://doi.org/10.1007/s40273-023-01279-2

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