Dataset Information

Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

ABSTRACT:

Background

In the randomised controlled trial ECHELON-2 (NCT01777152; January 2013), brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin and prednisone (CHP) demonstrated improved efficacy compared with CHOP (CHP and vincristine) in frontline CD30+ peripheral T-cell lymphoma (PTCL), an aggressive cancer with poor survival. In ECHELON-2, 70% of patients had systemic anaplastic large cell lymphoma (sALCL), a subtype of PTCL. Of sALCL patients who progressed from BV+CHP and CHOP, 36% (n = 17) and 56% (n = 36) received subsequent BV-containing therapy, respectively. As BV re-treatment was not funded in England at the time, our objective was to estimate adjusted efficacy and cost-effectiveness by excluding BV re-treatment from BV+CHP.

Methods

To remove the effects of BV re-treatment, the inverse probability of censoring weights (IPCW) and two-stage estimator (TSE) approaches, with and without re-censoring, were applied to overall survival (OS) in the BV+CHP arm of the ECHELON-2 sALCL population. Cost-effectiveness was determined in a three-state partitioned survival (PartSA) model from the perspective of the National Health Service (NHS) in England.

Results

The unadjusted hazard ratio (HR) for death in patients with sALCL with BV+CHP versus CHOP was 0.54 (95% CI 0.34, 0.87; p = 0.011). The model base case used TSE analysis without re-censoring, which provided an adjusted HR for death of 0.55 (95% CI 0.33, 0.86; p = 0.014). Incremental cost-effectiveness ratios (ICERs) including and excluding re-treatment with BV were £29,760/QALY and £27,761/QALY, respectively.

Conclusion

TSE without re-censoring provided the most clinically plausible estimate of survival whilst retaining sufficient information for OS extrapolation. After adjustment for BV re-treatment, BV+CHP remains an efficacious and cost-effective treatment in frontline sALCL compared with CHOP.

SUBMITTER: Cranmer H

PROVIDER: S-EPMC9596633 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

Cranmer Holly H Trueman David D Evers Elise E Woodcock Fionn F Podkonjak Tanja T

PharmacoEconomics - open 20220904 6

<h4>Background</h4>In the randomised controlled trial ECHELON-2 (NCT01777152; January 2013), brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin and prednisone (CHP) demonstrated improved efficacy compared with CHOP (CHP and vincristine) in frontline CD30+ peripheral T-cell lymphoma (PTCL), an aggressive cancer with poor survival. In ECHELON-2, 70% of patients had systemic anaplastic large cell lymphoma (sALCL), a subtype of PTCL. Of sALCL patients who progressed from BV+CHP and CHOP, 36 ...[more]

PMID: 36057890

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Project description:BackgroundTreatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) is a well-established therapy for advanced Hodgkin's lymphoma (HL). However, the recently completed ECHELON-1 trial showed potential net clinical benefit for brentuximab vedotin (BREN+AVD) compared to ABVD as frontline therapy in patients with advanced Hodgkin's lymphoma. The objective of this analysis is to determine whether, on current evidence, BREN+AVD is cost-effective relative to ABVD as frontline therapy in patients with advanced HL.MethodsWe constructed a probabilistic Markov model with two arms and six mutually exclusive health states, using six-month cycle lengths, and a 15-year time horizon. Time-dependent transition probabilities were calculated from 'real-world' data collected by the BC Cancer's Centre for Lymphoid Cancer database or from the literature for ABVD. Time-dependent transition probabilities for BREN+AVD were taken from the ECHELON-1 trial. We estimated the incremental cost and effects per patient of each therapy and calculated the incremental cost-effectiveness ratio (ICER). Costs were measured in 2018 Canadian dollars and effects measured in quality-adjusted life years (QALYs). A probabilistic analysis was used to generate a cost-effectiveness acceptability curve (CEAC).ResultsThe incremental cost between standard therapy with ABVD and therapy with BREN+AVD was estimated to be $192,336. The regimen of BREN+AVD resulted in a small benefit in terms of QALYs (0.46 QALYs). The estimated ICER was $418,122 per QALY gained. The probabilistic analysis suggests very few (8%) simulations fall below $100,000 per QALY. Even at a threshold of $200,000 per QALY gained, there was only a 24% chance that BREN+AVD would be considered cost-effective. Sensitivity analyses evaluating price reductions for brentuximab showed that these reductions needed to be in excess of 70% for this regimen to be cost-effective at a threshold of $100,000 per QALY.ConclusionsThere may be a clinical benefit associated with BREN+AVD, but on current evidence the benefit is not adequately substantive compared to ABVD therapy given the cost of brentuximab vedotin. Agencies responsible for making decisions about BREN+AVD as frontline therapy for patients with advanced HL should consider whether they are willing to implement this treatment given the current uncertainty and cost-benefit profile, or negotiate substantial price-reductions from the manufacturer should they choose to reimburse.

Dataset Information

Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

Background

Methods

Results

Conclusion

Publications

Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

Similar Datasets

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