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3428 A Prospective Economic Analysis of Canadian Cancer Trials Group Clc.2/Alliance A041202: A Randomized Phase III Comparison of Bendamustine-Rituximab Versus Ibrutinib-Based Regimens in Untreated Older Patients with Chronic Lymphocytic Leukemia

Program: Oral and Poster Abstracts
Session: 902. Health Services Research—Malignant Conditions (Lymphoid Disease): Poster III
Hematology Disease Topics & Pathways:
Adult, Leukemia, Biological, antibodies, CLL, Diseases, Therapies, enzyme inhibitors, Study Population, Lymphoid Malignancies, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Matthew C. Cheung, MD, MSc1, Nicole Mittmann, PhD2*, Carolyn Owen, MD FRCPC3, Nizar Abdel-Samad, MD4, Graeme Fraser5, Selay Lam, MD, BSc, FRCPC6, Michael Crump, MD7, Catherine Sperlich8*, Richard van der Jagt9, Stephen Couban, MD, BSc10, Jennifer A. Woyach, MD11, Amy S. Ruppert, PhD12, Allison M Booth13*, Sumithra J Mandrekar, PhD13*, Gail T. McDonald14*, Lois E. Shepherd14, Anca Prica, MD15, Hope Yen16*, Bingshu E. Chen14* and Annette E. Hay17

1Hematology/Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
2Sunnybrook Research Institute, Toronto, Canada
3Foothills Hospital & Tom Baker Cancer Ctr., Calgary, AB, Canada
4The Moncton Hospital, Moncton, NB, CAN
5Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada
6Department of Medicine, Division of Hematology, Western University, London Health Sciences Centre, London, ON, Canada
7Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
8Hopital Charles-Lemoyne, Longueuil, QC, CAN
9Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada
10Department of Hematology, Dalhousie University, Halifax, NS, Canada
11The Ohio State University Comprehensive Cancer Center, Columbus, OH
12Division of Hematology, The Ohio State University, Columbus, OH
13Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN
14Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
15Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
16Canadian Cancer Trials Group, Kingston, ON, Canada
17Canadian Cancer Trials Group, Cancer Research Institute, Kingston, ON, Canada

CCTG CLC.2/Alliance A041202 demonstrated superior progression-free survival at 2 years with ibrutinib alone (87%; HR 0.39) or ibrutinib-rituximab (IR 88%; HR 0.38) compared to chemo-immunotherapy with bendamustine-rituximab (BR 74%) in treatment-naïve patients (pts) with chronic lymphocytic leukemia (CLL) who were 65 or older (Woyach NEJM 2018). We hypothesized that ibrutinib-based therapies would be more costly than BR but that costs would be offset by less toxicity and improved quality of life (QOL). We completed a prospective trial-based economic analysis to study the direct medical costs and quality-adjusted benefit associated with ibrutinib-based therapies compared to BR in the Canadian (CDN) subset of patients enrolled in CLC.2/Alliance 041202.

All CDN pts were invited to participate in the companion analysis. Health utilities were collected using the EuroQOL EQ-5D and calculated using CDN population valuations (Bansback PLOS One 2012). Resource utilization forms were administered to collect off-protocol health care encounters. The planned analysis was a cost-utility analysis from the perspective of a public healthcare system, examining the costs and outcomes (quality-adjusted life years or QALYs) of ibrutinib-based therapy compared to BR. Unit costs were applied to resource data based on publicly available provincial/national databases; all costs were expressed in 2019 US dollars (1 CDN = 0.75 US dollar). Total and disaggregated direct medical costs are presented descriptively. Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months; derived utilities were used to calculate QALYs. A discount rate for costs and benefits (r=0.05) was applied. The analysis was based on estimation (with bootstrapping) of an incremental cost-effectiveness ratio (ICER) and/or direct medical costs.

A total of 55 pts were enrolled; two pts who did not receive any treatment were censored at day 1 and 3 after randomization and excluded from analysis. Of the 53 analysed, pt demographics were well balanced between treatments and were reflective of the entire population: mean age was 71.6 (SD 6.34) in pts receiving ibrutinib alone (n=17), 72.2 (SD 3.85) in pts receiving IR (n=18), and 71.7 (SD 4.1) in pts receiving BR (n=18). A total of 3 pts, one in each arm, had 17p deletion. Progression-free survival at 2 years for CDN pts was 94% (95% CI 65-99%) for ibrutinib, 100% (95% CI 100-100%) for IR, and 72% (95% CI 45-87%) for BR (Figure 1). At 24 months, 1 pt on the BR arm had crossed over to ibrutinib (as per protocol); there was no overall survival difference between the three arms. On-protocol costs (including protocol treatment, ambulatory care, and imaging) and off-protocol costs (including hospitalizations, concomitant medications, and ambulatory care) are highlighted in Figure 2. On-protocol costs were higher for pts receiving ibrutinib (mean $142,001 USD; SD 48,417) and IR ($164,931; SD 46,208) compared to BR ($38,509; SD 10,351), driven by higher drug acquisition costs associated with ibrutinib (list price $6422 for 420mg/30 days). In contrast, off-protocol costs were modestly higher for pts on BR (mean $3050; SD 3812) compared to the ibrutinib ($2460; SD 3863) or IR ($2890; SD 4206); hospitalizations were the key off-protocol cost drivers and were highest for pts on IR and BR. Overall mean costs over the 2-year time horizon were $144,461 (SD 47,910) for pts on ibrutinib, $167,820 (SD 46,830) for pts on IR, and $41,560 (SD 11,849) for pts on BR. Discounted 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. Given the similar quality-adjusted survival between arms at the time of this analysis, a formal ICER was not calculated.

Direct medical costs are substantially higher for pts receiving continuous ibrutinib-based therapies, compared to chemo-immunotherapy of fixed duration, in frontline CLL management; the key cost driver is the cost of ibrutinib. The PFS benefit with ibrutinib-based therapy has not translated into an advantage in quality-adjusted survival to date; further follow-up may be required to demonstrate any cost or QOL benefits associated with fewer progression events for those on ibrutinib.

Support: U10CA180821, U10CA180882; U10CA180863 and #704970 CCTG. https://acknowledgments.alliancefound.org ClinicalTrials.gov: NCT01886872

Disclosures: Owen: AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Lam: Roche: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Crump: Servier: Consultancy; Kite/Gilead: Consultancy; Roche: Consultancy. Sperlich: Lundbeck Canada: Honoraria. Woyach: Pharmacyclics, Janssen, Morphosys, Karyopharm, Verastem, Abbvie, Lox: Research Funding; Janssen, Pharmacyclics, AstraZeneca, Abbvie, Arqule: Consultancy; Pharmacyclics LLC, an AbbVie Company, AbbVie, Janssen, AstraZeneca, ArQule: Honoraria. Prica: astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria. Hay: Roche: Research Funding; Janssen: Research Funding.

*signifies non-member of ASH