Breast cancer is the most common malignant neoplasia in women in Spain (25,358 women were diagnosed with breast cancer in 2011 [101]), and the first cause of cancer-related mortality. Metastatic breast cancer (MBC) is estimated to occur in 20–30% of women with breast cancer [1].
Currently, MBC is, in most of cases, an in curable disease and treatment goals are primarily palliative and aimed at lengthening the time to disease progression, prolonging survival, reducing symptoms and improving the quality of life [2,3].
Adjuvant chemotherapy has been shown to reduce the risk of recurrence and prolong overall and disease-free survival [4]. The most frequently used groups of drugs in the adjuvant setting are anthracyclines and taxanes.
nab-paclitaxel (Abraxane®, Celgene, NJ, USA) is a nanoparticle albumin-bound paclitaxel (nab-paclitaxel) without solvent for injectable suspensions that permits the infusion of a dose of paclitaxel significantly higher than those used with paclitaxel formulated with solvents, and allows shorter infusion schedules without premedication. The favorable eff icacy and toxicity profile helps to focus treatment on the tumor [5,6].
nab-paclitaxel is indicated for the second-line treatment of MBC as monotherapy in women in whom other first-line antitumor treatments have failed and standard anthracycline therapy is not indicated.
The approved indication is based on the pivotal, randomized, controlled, Phase III
Emilio Alba1, Eva Ciruelos2, Rafael López3, José Manuel López-Vega4, Ana Lluch5, Miguel Martín6, Montserrat Muñoz7, Pedro Sánchez-Rovira8, Miguel Ángel Seguí9; COSTABRAX Working Group; Marta Rubio Liria10 and Ferran Pérez-Alcántara*11
1Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain 2Hospital 12 de Octubre, Madrid, Spain 3Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain 4Hospital Universitario Marqués de Valdecilla, Santander, Spain 5Hospital Clínic Universitari, Valencia, Spain 6Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain 7Hospital Clínic i Provincial, Barcelona, Spain 8Complejo Hospitalario de Jaén, Jaén, Spain 9Corporació Sanitaria Parc Taulí, Sabadell, Spain 10Celgene SL, Madrid, Spain 11Oblikue Consulting SL, Barcelona, Spain *Author for correspondence: Tel.: +34 932 521 377 Fax: +34 932 051 447 [email protected]
For a full list of the COSTABRAX Working Group, please see page 391
Aim: The COSTABRAX study evaluated the cost–effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) versus polyethylated castor oil-based standard paclitaxel (sb-paclitaxel) in the treatment of patients with previously treated metastatic breast cancer in Spain. Materials & methods: Efficacy data were obtained from the CA012 trial (nab-paclitaxel administered every 3 weeks [q3w] and sb-paclitaxel q3w) and indirect comparison (sb-paclitaxel administered weekly), and were modeled to a time horizon of 5 years using a Markov model. The analysis was performed from the National Health Service perspective. Use of resources and key assumptions of the model were validated by a panel of 22 local oncologists. Results: Compared with sb-paclitaxel q3w, nab-paclitaxel q3w was cost effective, with a cost per life year gained of €11,088 and a cost per quality-adjusted life year of €17,808. Compared with sb-paclitaxel administered weekly, it showed savings of €711 per patient. Conclusion: The COSTABRAX study showed that nab-paclitaxel q3w is a cost-effective alternative compared with sb-paclitaxel q3w and a cost-saving alternative to sb-paclitaxel administered weekly in Spain.
Keywords: breast • cancer • cost • COSTABRAX • nab-paclitaxel • Spain
Cost–utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel in monotherapy in pretreated metastatic breast cancer in SpainExpert Rev. Pharmacoecon. Outcomes Res. 13(3), 381–391 (2013)
ReviewResearch Report Alba, Ciruelos, López et al.
CA012 trial [7] in which nab-paclitaxel administered every 3 weeks (q3w) was compared with polyethylated castor oil-based standard paclitaxel (sb-paclitaxel) q3w. Based on the clinical and economic evidence, nab-paclitaxel was recommended by the health technology agencies of Scotland and Wales [102,103] for the approved indication.
The primary purpose of economic evaluation in healthcare is to provide valid and relevant information to healthcare policymakers and decision-makers regarding the relative value of alternative healthcare interventions, which is of special interest since the healthcare system faces a situation of limited resources.
The COSTABRAX study analyzed the cost–effectiveness of the treatment regimen of nab-paclitaxel q3w versus sb-paclitaxel q3w in patients with MBC in Spain. The analysis was based on the summary of product characteristics approved by the EMA.
In addition, since the panel of experts participating in the study indicated that the recommended administration schedule of sb-paclitaxel in Spain is weekly (qw), a second pharmacoeconomic analysis was also conducted comparing nab-paclitaxel q3w with sb-paclitaxel qw.
Materials & methodsPatientsThe population of the analysis was women with MBC in whom first-line antitumor treatments, including anthracyclines, had failed, or in whom anthracyclines were not indicated, as per licensed indication.
TreatmentsThe main analysis directly compared the therapeutic options from the pivotal Phase III trial by Gradishar et al. (2005) [7]:
Figure 1. The Markov model of disease evolution given the treatment option. M: Markov node; nab-paclitaxel: Nanoparticle albumin-bound paclitaxel; q3w: Every 3 weeks; qw: Weekly; sb-paclitaxel: Polyethylated castor oil-based standard paclitaxel.
Metastatic breast cancer
nab-paclitaxel q3w
sb-paclitaxel q3w/qw
Progression-free state
Progression-free state
Progression-free state
Disease-progression state
Disease-progression state
Disease-progression state
Disease-progression state
Death
DeathDeath
Death
Death
Alive
Alive
Progression-free state
Progression-free state
Progression-free state
Disease-progression state
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Disease-progression state
Death
DeathDeath
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M
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• nab-paclitaxel 260 mg/m2 infused intravenously (iv.) for 30 min and administered q3w.
• sb-paclitaxel 175 mg/m2 infused iv. for 3 h and administered q3w.
In addition, the study conducted a secondary analysis in which nab-paclitaxel q3w was compared with sb-paclitaxel 80 mg/m2 iv. for 1 h and administered qw due to its greater relevance to latest clinical practice with respect to sb-paclitaxel q3w. This analysis was conducted using an adjusted indirect comparison in the absence of studies directly comparing nab-paclitaxel q3w and sb-paclitaxel qw.
Type of analysisA pharmacoeconomic model was developed to compare the costs and effects of nab-paclitaxel q3w with both alternatives of treatment with sb-paclitaxel (q3w and qw). The incremental cost–effectiveness ratio (ICER) was calculated using Equation 1:
ICERCostnab
=( paclitaxelq w sbpaclitaxelCost
Effectivenes3 − )
( ss Effectivenessnabpaclitaxelq w sbpaclitaxel3 − ) (1)
Where Costnabpaclitaxelq3w
and Costsbpaclitaxel
represent the costs associated with nab-paclitaxel q3w and sb-paclitaxel (q3w or qw), respectively, and Ef fec t iveness
nabpac l i t a xe lq3w and
Effectivenesssbpaclitaxel
represent the clinical consequences in terms of life year gained (LYG) or quality-adjusted life years (QALYs) gained. The cost–effectiveness indicator is expressed as the incremental cost per LYG and the incremental cost per QALY gained with nab-paclitaxel q3w compared with sb-paclitaxel.
The analysis was performed from the perspective of the Spanish National Health Service considering only direct medical costs (e.g., cost of drugs, administration, adverse events [AEs] management and supportive care), with a time horizon of up to 5 years. All costs are expressed in 2011 euros. A discount rate of 3% was applied to future costs and outcomes according to the latest recommendations [8].
Description of the modelThe analysis used a Markov model to simulate the transition of the study population between different clinical states, reflecting the therapeutic regimen and survival, as well as estimating the effectiveness of the treatments compared and the accumulated costs. Markov models are the standard method used in cost–effectiveness studies to represent the natural history of diseases associated with
health conditions that change over time and present events related to the exposure of risks [9]. In these models, individuals can only remain in a specific state until, at the end of a defined period (3 weeks in this analysis), the patient may ‘transit’ between states (states with an associated cost and effectiveness).
The Markov model developed is defined by three health states that represent the evolution of treatment and survival of patients during the defined period. FigurE 1 shows a simplified diagram of the model. The progression-free state represents patients who respond to treatment, while nonresponders transit to the state of progression. From either of the two states, the patient has an associated risk of death.
Efficacy & transition probabilitiesThe clinical evidence used in this model was based on the results of the study CA012 [7], which examined the efficacy of nab-paclitaxel q3w versus sb-paclitaxel q3w in patients for single-agent paclitaxel therapy who had failed prior adjuvant or metastatic chemotherapy, had not received paclitaxel or docetaxel for treatment of metastatic carcinoma and had an Eastern Cooperative Oncology Group performance status of ≤2.
Figure 2. Efficacy of direct and indirect comparison of Nanoparticle albumin-bound paclitaxel administered every 3 weeks with paclitaxel administered weekly. (A) Hazard ratio–time to progression. (B) Hazard ratio–overall survival. HR: Hazard ratio; nab-paclitaxel: Nanoparticle albumin-bound paclitaxel; q3w: Every 3 weeks; qw: Weekly; sb-paclitaxel: Polyethylated castor oil-based standard paclitaxel. Data taken from [7,12].
sb-paclitaxelq3w
nab-paclitaxelq3w
sb-paclitaxelqw
Gradishar et al. [7]HR: 0.721(95% CI: 0.553–0.937)
Seidman et al. [12]HR: 0.699(95% CI: 0.584–0.837)
HR: 1.029(95% CI: 0.748–1.417)
sb-paclitaxelq3w
nab-paclitaxelq3w
sb-paclitaxelqw
Gradishar et al. [7]HR: 0.734(95% CI: 0.560–0.962)
ReviewResearch Report Alba, Ciruelos, López et al.
As per licensed indication, clinical evidence relates to the relevant subgroup analysis in patients with MBC who had previously failed first-line treatment for MBC (59% of patients in the CA012 study [7]). The subgroup analysis showed that nab-paclitaxel q3w had better overall survival (hazard ratio [HR]: 0.73; p = 0.024), survival free of disease progression, which was derived from the time to progression (HR: 0.73; p = 0.020) and higher response rates (27 vs 13%, respectively; p = 0.006) compared with sb-paclitaxel q3w.
The transition probabilities between different health states were obtained using the clinical data on overall survival and progression-free survival from the study CA012 using a Weibull parametric approximation to extrapolate efficacy data from the clinical trial.
This parameterization was considered as a valid approach as generated data consistent with empirical Kaplan–Meier estimates of survival obtained in the clinical trial [7]. The results of the Weibull approximation were adjusted for the corresponding HR of the alternatives compared (FigurE 2).
To compare the eff icacy of nab-paclitaxel q3w and sb-paclitaxel qw in the secondary analysis, adjusted indirect comparison methods were used due to the absence of studies directly comparing the two alternatives [10,11]. The indirect comparison was carried out using data from the study by Seidman et al. [12], which directly compared sb-paclitaxel q3w and qw treatment regimens. FigurE 2 shows the results of the indirect comparison carried out by calculating the HR for the time to progression (risk of progression) and overall survival (mortality risk).
The results of the indirect comparison show small nonsignificant differences in efficacy. This suggests that the efficacy of nab-paclitaxel q3w is not inferior to that of sb-paclitaxel qw, and therefore similar efficacy between the two alternatives was assumed, with the secondary analysis consisting of a cost minimization.
ToxicityThe model included grade III and IV AEs, which were those considered as economically relevant to the study (tablE 1).
Quality of lifeUtility values are used to represent the impact on quality of life associated with a particular health state on a scale of 0 (death) to 1 (perfect health). Assigning utility values to each health state of the model allowed calculation of the QALYs associated with
Table 1. Frequency of adverse events and associated costs.
Study (year) Adverse event(grades III and IV)
nab-paclitaxel q3w (%)
sb-paclitaxel q3w (%)
sb-paclitaxel qw (%)
Cost per event (€)
Ref.
Ojeda et al. (2003) Neutropenia 30.6 46.2 1.4 335 [27]
†It was assumed that this type of adverse event was not an additional cost of treatment and that management could be included in the routine cost of evaluation of the disease. nab-paclitaxel: Nanoparticle albumin-bound paclitaxel; q3w: Every 3 weeks; qw: Weekly; sb-paclitaxel: Polyethylated castor oil-based standard paclitaxel.
Table 2. Model utilities.
Utility corresponding to a specific health state
Health state Utility
Stable disease 0.65
Responder 0.81
Disease progression 0.45
Death 0
Reduction in utility due to adverse events
Adverse event Reduction in utility
Febrile neutropenia or infection 0.21
Adverse event in responders 0.14
Adverse event in stable patients 0.11
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each alternative compared. Similarly, a temporary reduction in the quality of life as a result of AE was considered.
Because data on the quality of life were not collected in the clinical trial, the utility data needed to estimate the corresponding QALYs were obtained from the literature (tablE 2) [13].
Resource use & costsThe analysis included direct medical costs. To identify and validate the use of resources, the opinion of a panel of clinical experts in oncology was consulted by means of a questionnaire and a subsequent face-to-face session. The unit costs were obtained from the literature and local databases.
To estimate the drug cost per cycle, a body surface area of 1.7 m2 was assumed. The prices included were ex-factory prices of the different treatment alternatives, assuming complete reuse of the vials (tablE 3). The price of sb-paclitaxel was extracted from the last generic and brand prices published at the Spanish reference price list [104] and the brand price of Abraxane from the General Council of Pharmacists Colleges database [105].
To calculate the costs associated with premedication, the administration of antiemetics for the group treated with nab-paclitaxel q3w, and the administration of antiemetics was included, dexamethasone, dexchlorpheniramine and ranitidine [105] for sb-paclitaxel qw and q3w (tablE 3). Given that day-hospital stay was identified as the main parameter differentiating the costs of administration of the alternatives, this was used to adjust the cost associated with the administration of chemotherapy based on the cost for sb-paclitaxel qw taken from the literature (tablE 3) [14].
The use of direct medical resources needed to estimate the costs associated with monitoring and general care of the disease were also obtained from expert opinion and valued according to unit costs (tablE 3) [106]. For patients in the terminal stage of the disease, a cost prior to death was assigned (tablE 3) [14].
Finally, the model included the costs for the occurrence of AEs (tablE 1), except for certain AEs that were assumed not to add to treatment costs and whose management would be included in the routine cost of monitoring and general care of the disease.
Sensitivity analysisTo assess the influence of parameter uncertainty on the results of the primary analysis and the robustness of the results, different sensitivity analyses were performed.
First, various univariate and multivariate sensitivity analyses were carried out on the results of the primary and secondary analyses in which the main cost parameters varied by ±20% (i.e., drug cost, cost of administration and AEs) and analyzed the influence of including prophylaxis for neutropenia. The results were presented as a tornado diagram (FigurE 3).
In addition, a probabilistic sensitivity analysis was performed using a second order Monte Carlo technique in a hypothetical cohort of 1000 patients [15]. Simulating the basic results of the model shows the probability that these remain stable during simultaneous variation of the key parameters included. This provides internal validation of the results, imputing a g-distribution for the costs, a normal distribution for the use of resources, a log-normal distribution for the HRs, relative risks
Drug cost/patient (cost [€] per cycle) 981.24 389.73 534.48
Premedication (cost [€] per cycle) 1.15 3.93 11.78
Administration of chemotherapy (cost [€] per cycle)‡ 217.50 435.01 783.03
Other costs
Disease monitoring
– Patients receiving chemotherapy (cost [€] per cycle of treatment)
– Patients who have finished chemotherapy (cost [€] each 3 months)
125.88
343.05
Cost of general care
– Patients without disease progression (cost [€] each 2 months)
– Patients with disease progression (monthly cost [€])220.16226.76
Cost (€) of the terminal phase of the disease§ 6051†Ex-factory price of nab-paclitaxel [105] and ex-factory generic and brand prices of sb-paclitaxel from the Spanish reference price list [104]. ‡Time of day-hospital occupancy (per cycle): nab-paclitaxel 1 h; sb-paclitaxel q3w 3.5 h; and sb-paclitaxel qw 4.5 h.§Data taken from [14]. nab-paclitaxel: Nanoparticle albumin-bound paclitaxel; q3w: Every 3 weeks; qw: Weekly; sb-paclitaxel: Polyethylated castor oil-based standard paclitaxel.
ReviewResearch Report Alba, Ciruelos, López et al.
and odds ratios, and a b-distribution of utilities and probabilities. The results of the probabilistic sensitivity analysis were expressed as a cost–effectiveness plane, in which the abscissae show incremental QALYs and the ordinates show incremental costs of nab-paclitaxel q3w versus sb-paclitaxel q3w. Each point shown in the plane corresponds to a simulation according to the stipulated parameters and distributions. The same plane shows the cost–effectiveness threshold commonly accepted in Spain (€30,000/QALY) [16–18].
ResultsThe results of the analysis are shown in tablE 4. The primary cost–effectiveness analysis shows that the mean LYG were 1.44 and 1.17 for nab-paclitaxel q3w and sb-paclitaxel q3w, respectively. The total cost was €16,447 and €13,509 for nab-paclitaxel q3w and sb-paclitaxel q3w, respectively. The ICER was €11,084 per LYG with nab-paclitaxel q3w. Using QALYs as a measure of effectiveness, the ICER was €17,808 per QALY.
In the secondary analysis of cost minimization, nab-paclitaxel q3w showed a mean saving of €711 per patient compared with sb-paclitaxel qw.
Results of the sensitivity analysisFigur E 3 shows that the most inf luential parameters in the univariate and multivariate analyses were the cost of administration and the drug costs of sb-paclitaxel in both the primary and secondary analyses. nab-paclitaxel q3w remained cost effective compared with sb-paclitaxel q3w, with an ICER ranging from €15,000 to 20,500 per QALY. In the secondary analysis (FigurE 3b), the tornado diagram also tends to confirm that nab-paclitaxel q3w was superior to sb-paclitaxel qw, with differences ranging from a saving of €1600 to a greater cost of €160.
The results of the probabilistic sensitivity analysis of nab-paclitaxel q3w compared with sb-paclitaxel q3w in terms of cost per QALY gained confirmed the robustness of the results, as shown
Figure 3. Univariate and multivariate sensitivity analysis: tornado diagram. (A) Primary analysis: nab-paclitaxel every 3 weeks versus sb-paclitaxel every 3 weeks. (B) Secondary analysis: nab-paclitaxel every 3 weeks versus sb-paclitaxel weekly (Abraxane® [Celgene, NJ, USA] vs paclitaxel weekly). nab-paclitaxel: Nanoparticle albumin-bound paclitaxel; QALY: Quality-adjusted life year; sb-paclitaxel: Polyethylated castor oil-based standard paclitaxel.
Administration cost of paclitaxel (-20%; +20%)
Drug cost of paclitaxel (-20%; +20%)
Cost of disease monitoring and general care (-20%; +20%)
Cost of monitoring and general care plus terminal phase of disease (-20%; +20%)Use of G-CSF (nab-paclitaxel 5% andsb-paclitaxel 0%; nab-paclitaxel 0% and sb-paclitaxel 5%)
Cost of adverse events (-20%; +20%)
Use of antiemetics (0%; 100%)
€0 €5000 €10,000 €15,000 €20,000 €25,000 €30,000
Base-case €17,808/QALY
Administration cost of paclitaxel (-20%; +20%)
Drug cost of paclitaxel (-20%; +20%)
Use of G-CSF (nab-paclitaxel 5% andsb-paclitaxel 0%; nab-paclitaxel 0% andsb-paclitaxel 5%)
ReviewResearch ReportCost–utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel
in FigurE 4. Using the previously defined threshold of efficiency, most simulations (85%) were located in the upper-right quadrant below the efficiency threshold, showing that nab-paclitaxel q3w was cost effective compared with sb-paclitaxel.
Expert commentaryThe primary study analysis showed that nab-paclitaxel q3w was cost effective compared with sb-paclitaxel q3w according to the commonly accepted threshold for the adoption of new technologies in Spain [16–18], as well as to the threshold based on the growth domestic product per capita recommended by the WHO [107]. The sensitivity analyses confirmed the robustness of the results. The secondary analysis showed nab-paclitaxel q3w was a less expensive alternative compared with sb-paclitaxel qw after cost minimization.
The COSTABRAX study is the first economic evaluation of nab-paclitaxel q3w as second-line treatment of MBC in Spain. The conclusions drawn from the results obtained for Spain are in line with those of the cost utility analyses conducted in the UK and Canada [19,20], in which nab-paclitaxel q3w was found to be a cost-effective alternative compared with sb-paclitaxel q3w and total cost per patient was lower with respect to docetaxel q3w. These results were used in the positive recommendations made by the rating agencies in Scotland and Wales [102,103]. Although nab-paclitaxel is not yet indicated as a first-line therapy, Dranitsaris, together with members of the Catalan Institute of Oncology, conducted a cost–utility study [21] based on the Phase II study [22] in which nab-paclitaxel was shown to be a cost-effective alternative compared with docetaxel for the first-line treatment
of patients with HER2-negative MBC previously exposed to anthracyclines. Using the results of the same Phase II trial [21], Dranitsaris et al. conducted a cost–effectiveness study in the UK [23] in which nab-paclitaxel 100 mg/m2 qw, 150 mg/m2 qw and 300 mg/m2 q3w regimens were compared with docetaxel 100 mg q3w. The results showed a cost per disease progression-free year gained of GB£5600, £31,800 and £9900, respectively, and concluded that nab-paclitaxel may be a first-line alternative to docetaxel q3w.
The efficiency gain demonstrated for nab-paclitaxel q3w in this study does not differ from the gain shown in other recent studies analyzing new MBC treatment alternatives. The combined treatment of lapatinib and capecitabine resulted with 0.19 QALYs gained compared with capecitabine alone [24]. Docetaxel q3w resulted with 0.24 extra QALYs compared with paclitaxel qw [14]. Bevacizumab plus paclitaxel qw resulted in 0.21 QALYs gained compared with paclitaxel qw [25]. nab-paclitaxel q3w resulted in 0.20 extra QALYs compared with sb-paclitaxel q3w in the Canadian setting [20].
A major limitation of this study is the nature of the nab-paclitaxel q3w comparators considered. The primary analysis was based on direct evidence comparing nab-paclitaxel q3w with sb-paclitaxel q3w, whose use in clinical practice has largely supplanted by the qw regimen in recent years. There is no direct evidence comparing nab-paclitaxel q3w with sb-paclitaxel qw, and therefore we used adjusted indirect comparison techniques, which should be treated with caution, as they present very large confidence intervals that tend to show nonsignificant differences [10,11]. However, direct and indirect comparisons tend to coincide,
Table 4. Cost–effectiveness results of nanoparticle albumin-bound paclitaxel administered every 3 weeks versus polyethylated castor oil-based standard paclitaxel administered every 3 weeks and polyethylated castor oil-based standard paclitaxel administered weekly.
ReviewResearch Report Alba, Ciruelos, López et al.
Figure 4. Probabilistic sensitivity analysis of nanoparticle albumin-bound paclitaxel every 3 weeks versus polyethylated castor oil-based standard paclitaxel every 3 weeks. QALY: Quality-adjusted life year.
although not always [11] and may even be less biased than direct comparisons [26]. The clinical development program of nab-paclitaxel has been extended with a randomized Phase II trial where different schedules qw and q3w (300 mg/m2 q3w, 150 mg/m2 qw and 100 mg/m2 qw) have demonstrated at least a trend for improved efficacy and reduced myelosuppression compared with docetaxel 100 mg/m2 q3w [21,22]. Future studies will provide further evidence and allow direct comparison of different regimens of nab-paclitaxel and docetaxel q3w. Further evidence is also needed in order to allow the comparison of qw schedules of nab-paclitaxel and sb-paclitaxel, which will be the most relevant comparison according to recent clinical practice.
In relation to the previous limitation, the regimen used for sb-paclitaxel qw in the study by Seidman et al. was 80 mg/m2 administered each week until disease progression without considering 1 week rest that may be used in clinical practice [12]. However, the authors of this article did not consider it because the conclusion of the adjusted indirect comparison was based on clinical outcomes from a published study and other information was not available.
The need to extrapolate survival data for a time horizon greater than the follow-up period of the clinical trial is another possible limitation of the analysis. Nevertheless, the parameters yielded consistent data in the estimated Kaplan–Meier survival curves.
Another limitation of the analysis arose from the fact that MBC patients may receive further treatment lines after progression post second-line treatment. This was not explicitly considered in the model due to complexity and limited data on both costs and outcomes of subsequent treatment lines. However, there is not a reason to consider that different chemotherapy regimens would be administered to patients depending on their previous
treatment – that is, it was assumed that subsequent treatment lines would not differ after either of the comparators in the present analysis.
Finally, the pharmaceutical costs of the alternatives may differ according to the health center considered, due to possible commercial discounts. This type of economic analysis cannot reflect these possible alternatives, and therefore the base case is based on the list prices reported by the health authorities [104]. Moreover, pharmaceutical costs may be different from one country to another and this should have a potential impact on the results. However, in the various sensitivity analyses carried out, variations in the price of sb-paclitaxel were considered yielding to the same conclusions of the analysis.
The formulation of nab-paclitaxel q3w allows the infusion of higher doses in a shorter time with a favorable toxicity profile. This represents a breakthrough in the treatment of MBC, in which the main
objective is to lengthen the time to disease progression and improve the quality of life of patients. The available clinical and economic information on nab-paclitaxel suggests it is an efficient alternative for the approved indication in the second-line treatment of MBC in adult patients who have failed first-line treatment of metastatic disease and in whom standard therapy with anthracyclines is not indicated.
ConclusionThe results of the COSTABRAX study in Spain showed that nab-paclitaxel q3w is a cost-effective alternative compared with sb-paclitaxel q3w, and a cost saving alternative versus sb-paclitaxel qw.
Five-year view A substantial proportion of patients with breast cancer eventually progress to metastatic disease. MBC has multiple clinical presentations and treatment should be selected according to the patient’s tumor characteristics, treatment history and performance status. The increased use of anthracyclines and taxanes in the earlier stages of disease makes treatment selection more challenging, and drug resistance often limits therapeutic options. Despite the trend toward targeted therapies, cytotoxic drugs remain a mainstay of MBC treatment and new therapies in that class are needed.
Several agents have clearly improved outcome either as mono-therapy or in combination regimens in the sequential treatment of patients with MBC. Further investigation of new and established drug therapies for breast cancer is enabling better definition of therapeutic targets, mechanisms of drug sensitivity and resistance, patients and therapy end points. Several emerging drug therapies have demonstrated promise in patients with
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ReferencesPapers of special note have been highlighted as:•ofinterest••ofconsiderableinterest
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2 Smigal C, Jemal A, Ward E et al. Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J. Clin. 56(3), 168–183 (2006).
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7 Gradishar WJ, Tjulandin S, Davidson N et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J. Clin. Oncol. 23(31), 7794–7803 (2005).
8 López Bastida J, Oliva J, Antoñanzas F et al. A proposed guideline for economic evaluation of health technologies. Gac. Sanit. 24(2), 154–170 (2010).
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12 Seidman AD, Berry D, Cirrincione C et al. Randomized Phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of cancer and leukemia group B protocol 9840. J. Clin. Oncol. 26(10), 1642–1649 (2008).
Key issues
• nab-paclitaxel is a nanoparticle albumin-bound paclitaxel without solvent for injectable suspensions indicated for second-line treatment of metastatic breast cancer as monotherapy. Its favorable efficacy and toxicity profile helps to focus treatment on the tumor.
• The COSTABRAX study is the first economic evaluation of nab-paclitaxel administered every 3 weeks as second-line treatment of metastatic breast cancer in Spain.
• The results of the COSTABRAX study in Spain showed that nab-paclitaxel administered every 3 weeks is a cost-effective alternative compared with polyethylated castor oil-based standard paclitaxel every 3 weeks, and a cost-saving alternative versus polyethylated castor oil-based standard paclitaxel administered weekly.
• The available clinical and economic information on nab-paclitaxel suggests it is an efficient alternative for the approved indication in the second-line treatment of metastatic breast cancer in adult patients who have failed first-line treatment of metastatic disease and in whom standard therapy with anthracyclines is not indicated.
MBC, and further progress in medical management is expected in the coming years.
It is hoped that the judicious use of novel and standard therapies will allow continued improvements in the management of patients with MBC. Because it is possible to extend the survival of MBC patients, the relative benefit of therapy in causing tumor regression and improvement in disease-related symptoms must be balanced with treatment-induced toxicity and the impact upon the patient’s quality of life. Cost–effectiveness issues are to become even more important, when both treatment costs and the number of lines of chemotherapy for the patients are expected to rise due to the better survival. Further work in the economics of MBC will be crucial to help guide treatment for patients living with this serious disease.
nab-paclitaxel displays good antitumor activity, has less toxicity than solvent–base paclitaxel and is a cost-effective alternative. These results have prompted initiation of several clinical trials, which are currently underway evaluating the role of nab-paclitaxel as a single agent or in combination with
cytotoxic and/or biologic agents in breast cancer and other solid tumors.
Financial & competing interests disclosureThis study was funded by Celgene (Madrid, Spain). Celgene employees were involved in the study design, in the edition and review of the manuscript, and in the decision to submit the manuscript for publication. This study was conducted by Oblikue Consulting (Barcelona, Spain), an independent consulting company, and received funds from Celgene. The expert members of the COSTABRAX Working Group received consulting fees from Celgene and have also acted as consultant /advisors for other pharmaceutical companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
The authors would like to acknowledge the contribution of C Crespo (Statistics Department, University of Barcelona, Spain) for his writing assistance and statistical support, which was funded by Oblikue Consulting.
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ReviewResearch ReportAlba, Ciruelos, López et al. Cost–utility analysis of nanoparticle albumin-bound paclitaxel versus paclitaxel
AffiliationsCOSTBRAX Working Group
• Emilio Alba Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain
• Isabel Álvarez Hospital de Donostia, San Sebastián, Spain
• José Ángel Arranz Hospital Gregorio Marañón, Madrid, Spain
• Agustí Barnadas Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
• Lourdes Calvo Complexo Hospitalario Universitario de A Coruña, La Coruña, Spain
• Eva Ciruelos Hospital 12 de Octubre, Madrid, Spain
• Javier Cortés Hospital Universitario del Vall d’Hebrón, Barcelona, Spain
• Juan de la Haba Hospital Reina Sofía, Córdoba, Spain
• Andrés García-Palomo Hospital Universitario de León, León, Spain
• Eva Guerra Hospital Universitario Ramón y Cajal, Madrid, Spain
• Antonio Llombart Hospital Arnau de Vilanova, Valencia, Spain
• Ana Lluch Hospital Clínic Universitari, Valencia, Spain
• Rafael López Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain
• José Manuel López-Vega Hospital Universitario Marqués de Valdecilla, Santander, Spain
• Guillermo López-Vivanco Hospital de Cruces, Bilbao, Spain
• Miguel Martín Instituto de Investigación Sanitaria Hospital Gregorio Marañón, Madrid, Spain
• Montserrat Muñoz Hospital Clínic i Provincial, Barcelona, Spain
• César Rodríguez Hospital Universitario de Salamanca, Salamanca, Spain
• Álvaro Rodríguez-Lescure Hospital General Universitario de Elche, Elche, Spain
• Pedro Sánchez-Rovira Complejo Hospitalario de Jaén, Jaén, Spain
• Miguel Ángel Seguí Corporació Parc Taulí, Sabadell, Spain
