The use of paclitaxel in the management of early stage breast cancer

Abstract

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of paclitaxel in the management of early stage breast cancer based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The scope was not clearly defined in the manufacturer's submission. Two of the three clinical trials included in the submission report showed that the addition of four cycles of paclitaxel to four cycles of doxorubicin and cyclophosphamide (AC-P) resulted in modest improvements in the two end points of diseasefree survival (DFS) and overall survival (OS). The third unpublished study evaluating four cycles of AC followed by paclitaxel or docetaxel in breast cancer did not show any statistically significant differences in DFS or OS between any group. The economic evaluation of paclitaxel for adjuvant therapy in early breast cancer was based on two of the three trials submitted as clinical evidence and used a probabilistic Markov state-transition model. The measure of health benefit was quality-adjusted life-years (QALYs) and the model included direct costs using a UK NHS perspective. The primary analysis compared AC-P with four cycles of AC. The reported incremental cost-effectiveness ratio (ICER) for this comparison was £4726 per additional QALY for AC-P compared with four cycles of AC. The submission did not include a DOI: 10.3310/hta13suppl1/03The use of paclitaxel in the management of early stage breast cancer 16 systematic review for clinical or cost-effectiveness evidence. As a result, potentially relevant trials and previously published studies were omitted. The main comparator used did not represent standard care in the UK NHS and a large number of relevant comparators were omitted, including docetaxel. The manufacturer did not consider potentially important patient subgroups defined by baseline risk, and the cost-effectiveness result in the average overall patient population may conceal important variation between subgroups. Overall, although the economic model may have indicated that the addition of four cycles of paclitaxel to four cycles of AC may be cost-effective compared with providing four cycles of AC only, this comparison is not informative to current clinical practice in the UK NHS. In the context of this review it is not possible for the ERG to predict the cost-effectiveness of paclitaxel compared with more appropriate, and potentially more effective, relevant comparators. The guidance issued by NICE in July 2006 as a result of the STA states that paclitaxel is not recommended as an option for the adjuvant treatment of women with early nodepositive breast cancer.

Essential medicines for breast cancer in low and middle income countries

“…This might be attributable to their late inclusion in the WHO model list in 2011; it needs additional time before medicines appear on the majority of NEMLs. Besides, in the years prior to 2011, affordability of taxanes was of concern for healthcare systems in LMICs [ 29 – 31 ].…”

The clinical effectiveness and cost-effectiveness of different surveillance mammography regimens after the treatment for primary breast cancer: systematic reviews registry database analyses and economic evaluation.

“…The costs of further invasive tests were obtained from a NICE evidence review group (ERG) report 96 and inflated to current prices using the PSSRU inflation index. was based on the same source, and inflated to 2008 prices.…”

Survival Time Outcomes in Randomized, Controlled Trials and Meta-Analyses: The Parallel Universes of Efficacy and Cost-Effectiveness

“…The summary statistics in the synthesis were pooled (log) hazard ratios (7) or (log) relative risks (3) ( Table 3) ( [21][22][23][24][25][26][27][28][29][30][31]. To carry out CEAs, these hazard or risk ratios were again applied to "baseline" parametric models estimated mostly from the baseline in the manufacturer's trial.…”

“…This could improve the accuracy of the review we have conducted and would certainly offer rich insights into how the analyses were motivated and used, but it would be unlikely to change the conclusions of this study. In cases in which de novo survival analyses were undertaken by the evidence review group [8,11,15,26], one looked at further parametric curves, two examined the area under the KM curve, and one used external data. It is therefore unlikely that further examination of our sample of studies would change our conclusions.…”