Matthew C Cheung1, Nicole Mittmann2, Carolyn Owen3, Nizar Abdel-Samad4, Graeme A M Fraser5, Selay Lam6, Michael Crump7, Catherine Sperlich8, Richard van der Jagt9, Anca Prica7, Stephen Couban10, Jennifer A Woyach11, Amy S Ruppert12, Allison M Booth13, Sumithra J Mandrekar14, Gail McDonald15, Lois E Shepherd16, Hope Yen15, Bingshu E Chen15, Annette E Hay17. 1. Division of Hematology, Department of Medicine, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada; Canadian Cancer Trials Group, Queens University, Kingston, Canada. Electronic address: matthew.cheung@sunnybrook.ca. 2. Canadian Cancer Trials Group, Queens University, Kingston, Canada; Department of Pharmacology and Toxicology and Institute for Health Policy Management and Evaluation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. 3. Foothills Medical Centre and Tom Baker Cancer Centre, Calgary, Canada. 4. Division of Hematology, The Moncton Hospital, Moncton, Canada. 5. Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Canada. 6. Victoria Hospital, Western University, London, Canada. 7. Canadian Cancer Trials Group, Queens University, Kingston, Canada; Division of Hematology, Department of Medicine, Princess Margaret Hospital and University of Toronto, Toronto, Canada. 8. Centre integre de Santé et de Services Sociaux de la Montérégie-Centre, Greenfield Park, Canada. 9. Hematology, Ottawa Hospital, University of Ottawa, Ottawa, Canada. 10. Canadian Cancer Trials Group, Queens University, Kingston, Canada; Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Canada. 11. Division of Hematology, The Ohio State University, Columbus, OH. 12. Division of Hematology, The Ohio State University, Columbus, OH; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN. 13. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN; Department of Quantitative Health Sciences, and Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN. 14. Department of Quantitative Health Sciences, and Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN. 15. Canadian Cancer Trials Group, Queens University, Kingston, Canada. 16. Department of Pharmacology and Toxicology and Institute for Health Policy Management and Evaluation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. 17. Canadian Cancer Trials Group, Queens University, Kingston, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Abstract
INTRODUCTION: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies. METHODS: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy. RESULTS: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; P < 0.0001) and IR (mean $219,908; P < 0.0001) compared to BR (mean $51,345), driven by higher acquisition costs for ibrutinib. Total mean costs (over 2-years) were $192,615 with ibrutinib, $223,761 with IR, and $55,413 with BR (P < 0.0001 for ibrutinib vs. BR and P < 0.0001 for IR vs. BR). QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR; therefore, a formal cost-utility analysis was not conducted. CONCLUSIONS: Direct medical costs are higher for patients receiving ibrutinib-based therapies compared to chemoimmunotherapy in frontline chronic lymphocytic leukemia, with the cost of ibrutinib representing a key driver.
INTRODUCTION: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies. METHODS: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy. RESULTS: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; P < 0.0001) and IR (mean $219,908; P < 0.0001) compared to BR (mean $51,345), driven by higher acquisition costs for ibrutinib. Total mean costs (over 2-years) were $192,615 with ibrutinib, $223,761 with IR, and $55,413 with BR (P < 0.0001 for ibrutinib vs. BR and P < 0.0001 for IR vs. BR). QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR; therefore, a formal cost-utility analysis was not conducted. CONCLUSIONS: Direct medical costs are higher for patients receiving ibrutinib-based therapies compared to chemoimmunotherapy in frontline chronic lymphocytic leukemia, with the cost of ibrutinib representing a key driver.
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