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Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective

Clarke, CS; Hunter, RM; Shemilt, I; Serra-Sastre, V; (2017) Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective. PLoS One , 12 (3) , Article e0172731. 10.1371/journal.pone.0172731. Green open access

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Abstract

BACKGROUND: Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. METHODS AND FINDINGS: Network meta-analysis (NMA) was used to examine which trials' data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks' trastuzumab is cost-saving and leads to more QALYs than 12 months', i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. CONCLUSIONS: Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks' with 14 months' trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials' data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results.

Type: Article
Title: Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0172731
Publisher version: http://dx.doi.org/10.1371/journal.pone.0172731
Language: English
Additional information: Copyright: © 2017 Clarke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1543351
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