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The American Journal of Managed Care February 2020
Care Coordination for Veterans With COPD: A Positive Deviance Study
Ekaterina Anderson, PhD; Renda Soylemez Wiener, MD, MPH; Kirsten Resnick, MS; A. Rani Elwy, PhD; and Seppo T. Rinne, MD, PhD
Expand Predeductible Coverage Without Increasing Premiums or Deductibles
A. Mark Fendrick, MD
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Jeffrey D. Dunn, PharmD, MBA
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Risk Adjustment in Home Health Care CAHPS
Lisa M. Lines, PhD, MPH; Wayne L. Anderson, PhD; Harper Gordek, MPH; and Anne E. Kenyon, MBA
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Hsueh-Fen Chen, PhD; J. Mick Tilford, PhD; Robert F. Schuldt, MA; and Fei Wan, PhD
Preventive Drug Lists as Tools for Managing Asthma Medication Costs
Melissa B. Gilkey, PhD; Lauren A. Cripps, MA; Rachel S. Gruver, MPH; Deidre V. Washington, PhD; and Alison A. Galbraith, MD, MPH
Co-payment Policies and Breast and Cervical Cancer Screening in Medicaid
Lindsay M. Sabik, PhD; Anushree M. Vichare, PhD; Bassam Dahman, PhD; and Cathy J. Bradley, PhD
Discontinuation of New Hepatitis C Drugs Among Medicare Patients
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Tricia Johnson, PhD; Surrey Walton, PhD; Stacie Levine, MD; Erik Fister, MA; Aliza Baron, MA; and Sean O’Mahony, MB, BCh, BAO
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Cost-effectiveness of Brentuximab Vedotin With Chemotherapy in Treatment of CD30-Expressing PTCL
Tatyana Feldman, MD; Denise Zou, MA; Mayvis Rebeira, PhD; Joseph Lee, PhD; Michelle Fanale, MD; Thomas Manley, MD; Shangbang Rao, PhD; Joseph Feliciano, PharmD; Mack Harris, BA; and Anuraag Kansal, PhD
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Medical Utilization Surrounding Initial Opioid-Related Diagnoses by Coding Method
Amber Watson, PharmD; David M. Simon, PhD; Meridith Blevins Peratikos, MS; and Elizabeth Ann Stringer, PhD

Cost-effectiveness of Brentuximab Vedotin With Chemotherapy in Treatment of CD30-Expressing PTCL

Tatyana Feldman, MD; Denise Zou, MA; Mayvis Rebeira, PhD; Joseph Lee, PhD; Michelle Fanale, MD; Thomas Manley, MD; Shangbang Rao, PhD; Joseph Feliciano, PharmD; Mack Harris, BA; and Anuraag Kansal, PhD
An economic model based on the ECHELON-2 trial demonstrated cost-effectiveness of brentuximab vedotin with chemotherapy in frontline treatment of CD30-expressing peripheral T-cell lymphoma (PTCL).
ABSTRACT

Objectives: To evaluate the cost-effectiveness of brentuximab vedotin (Adcetris) in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in the first-line setting for CD30-expressing peripheral T-cell lymphoma (PTCL).

Study Design: An economic model was developed using clinical and quality-of-life (QOL) data from the ECHELON-2 trial, in which A+CHP demonstrated significant improvement in progression-free survival (PFS) and overall survival (OS) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

Methods: A partitioned survival model, consisting of 3 health states (PFS, postprogression survival, and death), was constructed from a US payer perspective over a lifetime time horizon. PFS and OS observed from ECHELON-2 were extrapolated using standard parametric distributions. The best-fitting distributions (log-normal for both arms) were selected based on statistical goodness of fit and clinical plausibility of the long-term projections. Utilities were based on the European Quality of Life 5-Dimensional data collected in ECHELON-2. Medical resource use and costs were from literature and standard sources.

Results: The model predicted that A+CHP extended PFS and OS by 2.92 and 3.38 years, respectively, over CHOP. After incorporating QOL and discounting, A+CHP was associated with 1.79 quality-adjusted life-years gained at a total incremental cost of $159,388, resulting in an incremental cost-effectiveness ratio (ICER) of $89,217. Sensitivity analyses provided ICERs ranging approximately from $57,000 to $138,000. The estimated probability that A+CHP is cost-effective compared with CHOP was 82% at a willingness-to-pay threshold of $150,000.

Conclusions: Based on the ECHELON-2 trial data, this analysis found A+CHP to be cost-effective for patients with previously untreated CD30-expressing PTCL.

Am J Manag Care. 2020;26(2):e41-e49. https://doi.org/10.37765/ajmc.2020.42400
Takeaway Points

This cost-effectiveness evaluation, which used the data from the ECHELON-2 trial, demonstrates that the economic value for adopting brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL) is within the widely accepted range for oncology medicines.
  • The analysis of ECHELON-2 projected significant differences in long-term survival in favor of A+CHP versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP): 2.92 years in progression-free survival, and 3.38 years in overall survival.
  • In a wide range of sensitivity analyses, the incremental cost-effectiveness ratio of A+CHP compared with CHOP fell below $150,000 per quality-adjusted life-year gained.
  • The sensitivity reflects that the central driver of value of brentuximab vedotin treatment in this population is extended survival.
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of mostly aggressive non-Hodgkin lymphomas (NHLs) that result from the clonal proliferation of mature postthymic lymphocytes, including natural killer (NK) cell neoplasms.1 The more than 25 PTCL subtypes account for approximately 10% of NHL cases in the United States and Europe and may account for up to 24% in Asia. According to the World Health Organization classification of T-cell malignancies, there were approximately 7000 new cases of mature T-/NK-cell lymphoid neoplasms in the United States in 2016.2

The frontline treatment landscape for PTCL varies by subtype. The 3 most common subtypes—PTCL–not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and systemic anaplastic large cell lymphoma (sALCL)—are usually treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens.3-5 However, these regimens are associated with disappointing efficacy, including low rates of complete remission, poor progression-free survival (PFS), and poor overall survival (OS).6-8 The International PTCL Project reported 5-year OS for PTCL-NOS, AITL, ALK-negative ALCL, and ALK-positive ALCL to be 32%, 32%, 49%, and 70%, respectively.9 Clinical studies adding active agents to the CHOP regimen have shown limited efficacy improvements,10 demonstrating the high unmet need in these patients.

Brentuximab vedotin (Adcetris; Seattle Genetics, Inc; Bothell, WA) is a CD30-directed antibody-drug conjugate approved for several indications, including previously untreated sALCL or other CD30-expressing PTCLs when used in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP).11

ECHELON-2 (ClinicalTrials.gov NCT01777152) is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase 3 trial comparing A+CHP with CHOP in patients with previously untreated CD30-expressing PTCL. The PFS hazard ratio (HR) was 0.71 (95% CI, 0.54-0.93; P = .0110) for the A+CHP group versus the CHOP group. After a median follow-up of 36.2 months (95% CI, 35.9-41.8 months), the median PFS in the A+CHP group was longer than that in the CHOP group: 48.2 months (95% CI, 35.2 months–not evaluable) versus 20.8 months (95% CI, 12.7-47.6 months), respectively; P = .0110.12 Treatment with A+CHP reduced the risk of death by 34% compared with CHOP (HR, 0.66; 95% CI, 0.46-0.95; P = .0244); after a median follow-up of 42.1 months, the 75th percentile OS was not reached in the A+CHP group but was 17.5 months in the CHOP group. Adverse events (AEs) in both arms were similar and manageable.12

PTCL and other aggressive NHLs incur substantial healthcare resource utilization and high medical costs driven by hospitalizations, pharmacy services, and outpatient office visits.13,14 For patients to be able to access new therapies, data are required to quantify their overall clinical benefits and incremental costs compared with current treatments. The objective of this study was to quantify the incremental benefits and costs of A+CHP compared with CHOP in patients with newly diagnosed CD30-expressing PTCL, from a US healthcare payer perspective, using a cost-effectiveness model.

METHODS

Patients

The model considered a patient cohort that was aligned with the eligible patients included in ECHELON-2.12 The trial allowed enrollment of 7 PTCL subtypes that may express CD30: sALCL (70%), PTCL-NOS (16%), AITL (12%), and others (2%).12

Model Overview

The model was developed in Microsoft Excel using the partitioned survival approach, which is commonly used for therapeutic interventions for cancers. The model projects the fraction of a fixed cohort in each of 3 health states—PFS, postprogression survival (PPS), and death—over time. To estimate these fractions, parametric survival functions were used to estimate the proportion of the cohort remaining free of the end points that defined the relevant health states (eAppendix Figure [eAppendix available at ajmc.com]). Time in the PFS state was estimated directly from the area under the PFS curves, whereas time in the PPS state was estimated by the area between the PFS and OS curves based on analyses of survival data from ECHELON-2. Because the patient population is modeled as a single cohort throughout the time horizon, the efficacy of subsequent treatments is implicitly captured in the OS data. As such, only their costs need to be captured explicitly based on the actual subsequent treatments received in ECHELON-2.

Costs and clinical outcomes were estimated at fixed time points based on the proportion of the cohort in each health state at a given time. The model utilized a 21-day cycle and was run for a lifetime time horizon over which costs and health outcomes were evaluated, with a discounting rate of 3% per annum.15 The base-case analysis takes the perspective of a third-party commercial payer in the United States.

Model inputs are summarized in Table 1 [part A and part B].13,16-23 The main assumptions are described in the subsections that follow.


 
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