Cost-effectiveness of capecitabine and bevacizumab maintenance treatment after first-line induction treatment in metastatic colorectal cancer

Franken, Mira D.; Rooijen, E.M. van; May, Anne M.; Koffijberg, Hendrik; Tinteren, Harm van; Mol, Linda; Tije, Albert J. ten; Creemers, Geert-Jan; Velden, Ankie M.T. van der; Tanis, Bea C.; Groot, Carin A Uyl-de; Punt, Cornelis J.A.; Koopman, Miriam; Oijen, Martijn G.H. van

doi:10.1016/j.ejca.2017.01.019

Cited by 25 publications

(28 citation statements)

References 30 publications

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“…The recent study of Franken et al [ 22 ] evaluated the cost-effectiveness of capecitabine and bevacizumab (CAP-B) maintenance compared with the observational strategy following first-line capecitabine, oxaliplatin and bevacizumab (CAPOX-B) induction treatment for mCRC patients with stable disease or better after 6 cycles of treatment. CAP-B maintenance compared with observation resulted in an ICER of €175,452 per quality-adjusted life years (QALY) and €204,694 per life year (LY).…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic colorectal cancer in a public hospital school

et al. 2017

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BackgroundMetastatic colorectal cancer imposes a substantial burden on patients and society. Over the last years, progresses in the treatment have been made especially due to the introduction of monoclonal antibodies, such as bevacizumab which, on the other hand, has considerably increased the costs of treatment. We performed a cost-effectiveness analysis of bevacizumab plus XELOX in comparison with XELOX alone in metastatic colorectal cancer in first-line therapy, from the perspective of a public hospital school in Brazil.MethodsThis was a cost-effectiveness analysis performed by a decision tree and Markov models. Costs were expressed in local currency and outcomes were expressed in months of life gained. The model was constructed using the TreeAge Pro 2013® software.ResultsThe incremental difference in years of life gained was 2.25 months, with an extra cost of 47,833.57 BRL, resulting in an incremental cost-effectiveness of 21,231.43 BRL per month of life gained.ConclusionsAlthough the XELOX plus bevacizumab regimen is a more expensive and more effective treatment than XELOX, it does not fit the reimbursement values fixed by the public healthcare system in Brazil.

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Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic colorectal cancer in a public hospital school

et al. 2017

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“…In the United States, the capecitabine and bevacizumab maintenance therapy ICER of $725 601 per QALY is more than 3.3 times that in the Netherlands. If the higher incremental QALY of 0.21 is used (as reported in a Dutch population), 6 the cost-effectiveness of the maintenance therapy in the United States is still 2.3 times worse ($501 033/QALY). Differences in capecitabine and bevacizumab drug costs in the United States and the Netherlands explain this discrepancy.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

“…5 While capecitabine and bevacizumab maintenance therapy doubled the time to a first progression event compared with observation, the CAIRO3 RCT did not consider the additional costs associated with maintenance therapy. Recently, Franken et al 6 performed a cost-effectiveness analysis, finding that maintenance therapy conferred 0.21 quality-adjusted life-years (QALYs) at an incremental costeffectiveness ratio (ICER) of €175,452 per QALY. Whether these results apply to the United States remains unknown.…”

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confidence: 99%

Cost-effectiveness of Maintenance Capecitabine and Bevacizumab for Metastatic Colorectal Cancer

et al. 2019

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IMPORTANCE Unregulated drug prices increase cancer therapy costs. After induction chemotherapy, patients with metastatic colon cancer can receive maintenance capecitabine and bevacizumab therapy based on improved progression-free survival, but whether this treatment's cost justifies its benefits has not been evaluated in the United States. OBJECTIVE This study sought to determine the influence of capecitabine and bevacizumab drug prices on cost-effectiveness from a Medicare payer's perspective. DESIGN, SETTING, AND PARTICIPANTS The incremental cost-effectiveness of capecitabine and bevacizumab maintenance therapy was determined with a Markov model using a quality-of-life penalty based on outcomes data from the CAIRO phase 3 randomized clinical trial (RCT), which included 558 adults in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. The outcomes were modeled using Markov chains to account for patients who had treatment complications or cancer progression. Transition probabilities between patient states were determined, and each state's costs were determined using US Medicare data on payments for capecitabine and bevacizumab treatment. Deterministic and probabilistic sensitivity analyses identified factors affecting cost-effectiveness. MAIN OUTCOMES AND MEASURES Life-years gained were adjusted using CAIRO3 RCT quality-of-life data to determine quality-adjusted life-years (QALYs). The primary end point was the incremental cost-effectiveness ratio, representing incremental costs per QALY gained using a capecitabine and bevacizumab maintenance regimen compared with observation alone. RESULTS Markov model estimated survival and complication outcomes closely matched those reported in the CAIRO3 RCT, which included 558 adults (n = 197 women, n = 361 men; median age, 64 and 63 years for patients in the observation and maintenance therapy groups, respectively) in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. Incremental costs for a 3-week maintenance chemotherapy cycle were $6601 per patient. After 29 model iterations corresponding to 60 months of follow-up, mean per-patient costs were $105 239 for maintenance therapy and $21.10 for observation. Mean QALYs accrued were 1.34 for maintenance therapy and 1.20 for observation. The incremental cost-effectiveness ratio favored maintenance treatment, at an incremental cost of $725 601 per QALY. The unadjusted ratio was $438 394 per life-year. Sensitivity analyses revealed that cost-effectiveness varied with changes in drug costs. To achieve an incremental cost-effectiveness ratio of less than $59 039 (median US household income) per unadjusted life-year would require capecitabine and bevacizumab drug costs to be reduced from $6173 (current cost) to $452 per 3-week chemotherapy cycle. CONCLUSIONS AND RELEVANCE Antineoplastic therapy is expensive for payers and society. The price of capecitabine and bevacizumab mainten...

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“…A previous developed DES model was adapted to use the sets of distributions’ parameter values generated by the Bootstrap and MVNorm approach in the PSA (Additional file 1 ). The model was developed and validated in AnyLogic multimethod simulation software [ 24 ] according to good research practices guidelines [ 7 , 25 , 26 ], and structured according to the same health states as the state-transition model used for the original evaluation of the CAIRO3 study: post-induction, re-induction, salvage, and death [ 27 ] (Fig. 4 ).…”

Section: Methodsmentioning

confidence: 99%

“…Parameters of the distributions used to reflect parameter uncertainty in non-time-to-event parameters, e.g. costs and utilities, were deliberately defined exactly as in the original evaluation of the CAIRO3 study for all subgroups [ 27 ], so that observed differences in outcomes could be designated specifically to the uncertainty in time-to-event distributions’ parameter estimates. The health economic outcomes for all case study analyses were presented in incremental cost-effectiveness planes and CEACs based on 10,000 PSA runs of 10,000 patients per treatment strategy.…”

Section: Methodsmentioning

confidence: 99%

Accounting for parameter uncertainty in the definition of parametric distributions used to describe individual patient variation in health economic models

Degeling

IJzerman

Koopman

et al. 2017

BMC Med Res Methodol

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BackgroundParametric distributions based on individual patient data can be used to represent both stochastic and parameter uncertainty. Although general guidance is available on how parameter uncertainty should be accounted for in probabilistic sensitivity analysis, there is no comprehensive guidance on reflecting parameter uncertainty in the (correlated) parameters of distributions used to represent stochastic uncertainty in patient-level models. This study aims to provide this guidance by proposing appropriate methods and illustrating the impact of this uncertainty on modeling outcomes.MethodsTwo approaches, 1) using non-parametric bootstrapping and 2) using multivariate Normal distributions, were applied in a simulation and case study. The approaches were compared based on point-estimates and distributions of time-to-event and health economic outcomes. To assess sample size impact on the uncertainty in these outcomes, sample size was varied in the simulation study and subgroup analyses were performed for the case-study.ResultsAccounting for parameter uncertainty in distributions that reflect stochastic uncertainty substantially increased the uncertainty surrounding health economic outcomes, illustrated by larger confidence ellipses surrounding the cost-effectiveness point-estimates and different cost-effectiveness acceptability curves. Although both approaches performed similar for larger sample sizes (i.e. n = 500), the second approach was more sensitive to extreme values for small sample sizes (i.e. n = 25), yielding infeasible modeling outcomes.ConclusionsModelers should be aware that parameter uncertainty in distributions used to describe stochastic uncertainty needs to be reflected in probabilistic sensitivity analysis, as it could substantially impact the total amount of uncertainty surrounding health economic outcomes. If feasible, the bootstrap approach is recommended to account for this uncertainty.Electronic supplementary materialThe online version of this article (doi: 10.1186/s12874-017-0437-y) contains supplementary material, which is available to authorized users.

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Cost-effectiveness of capecitabine and bevacizumab maintenance treatment after first-line induction treatment in metastatic colorectal cancer

Cited by 25 publications

References 30 publications

Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic colorectal cancer in a public hospital school

Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic colorectal cancer in a public hospital school

Cost-effectiveness of Maintenance Capecitabine and Bevacizumab for Metastatic Colorectal Cancer

Accounting for parameter uncertainty in the definition of parametric distributions used to describe individual patient variation in health economic models

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