Dataset Information

Cost-effectiveness of brentuximab vedotin in advanced stage Hodgkin’s lymphoma: a probabilistic analysis

ABSTRACT: Background Treatment 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. Methods We 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). Results The 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. Conclusions There 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.

SUBMITTER: Raymakers A

PROVIDER: S-EPMC7557030 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundBrentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma.MethodsWe conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival.ResultsAt a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.ConclusionsA+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).

Project description:BackgroundIn adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear.MethodsWe conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed.ResultsOf 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group.ConclusionsThe addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.).

Dataset Information

Cost-effectiveness of brentuximab vedotin in advanced stage Hodgkin’s lymphoma: a probabilistic analysis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets