Cost Analysis of Albumin-Bound Paclitaxel vs Paclitaxel
The 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, as well as to the threshold based on the growth domestic product per capita recommended by the WHO. 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, 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. 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 based on the Phase II study 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, Dranitsaris et al. conducted a cost–effectiveness study in the UK in which nab-paclitaxel 100 mg/m qw, 150 mg/m qw and 300 mg/m q3w regimens were compared with docetaxel 100 mg q3w. The results showed a cost per disease progressionfree year gained of GBP£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. Docetaxel q3w resulted with 0.24 extra QALYs compared with paclitaxel qw. Bevacizumab plus paclitaxel qw resulted in 0.21 QALYs gained compared with paclitaxel qw. nab-paclitaxel q3w resulted in 0.20 extra QALYs compared with sb-paclitaxel q3w in the Canadian setting.
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. However, direct and indirect comparisons tend to coincide, although not always and may even be less biased than direct comparisons. The clinical development program of nab-paclitaxel has been extended with a randomized Phase II trial where different schedules qw and q3w (300 mg/m q3w, 150 mg/m qw and 100 mg/m qw) have demonstrated at least a trend for improved efficacy and reduced myelosuppression compared with docetaxel 100 mg/m q3w. 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/m administered each week until disease progression without considering 1 week rest that may be used in clinical practice. 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. 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.
Expert Commentary
The 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, as well as to the threshold based on the growth domestic product per capita recommended by the WHO. 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, 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. 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 based on the Phase II study 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, Dranitsaris et al. conducted a cost–effectiveness study in the UK in which nab-paclitaxel 100 mg/m qw, 150 mg/m qw and 300 mg/m q3w regimens were compared with docetaxel 100 mg q3w. The results showed a cost per disease progressionfree year gained of GBP£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. Docetaxel q3w resulted with 0.24 extra QALYs compared with paclitaxel qw. Bevacizumab plus paclitaxel qw resulted in 0.21 QALYs gained compared with paclitaxel qw. nab-paclitaxel q3w resulted in 0.20 extra QALYs compared with sb-paclitaxel q3w in the Canadian setting.
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. However, direct and indirect comparisons tend to coincide, although not always and may even be less biased than direct comparisons. The clinical development program of nab-paclitaxel has been extended with a randomized Phase II trial where different schedules qw and q3w (300 mg/m q3w, 150 mg/m qw and 100 mg/m qw) have demonstrated at least a trend for improved efficacy and reduced myelosuppression compared with docetaxel 100 mg/m q3w. 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/m administered each week until disease progression without considering 1 week rest that may be used in clinical practice. 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. 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.
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