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Lapatinib and Trastuzumab in Combination with an Aromatase Inhibitor for the First-Line Treatment of Metastatic Hormone Receptor-Positive Breast Cancer which Over-Expresses Human Epidermal Growth Factor 2 (HER2): A Systematic Review and Economic Analysis

Health Technology Assessment, No. 15.42

N Fleeman, A Bagust, A Boland, R Dickson, Y Dundar, M Moonan, J Oyee, M Blundell, H Davis, A Armstrong, and N Thorp.

Author Information

N Fleeman,1 A Bagust,1 A Boland,1 R Dickson,1,* Y Dundar,1 M Moonan,2 J Oyee,1 M Blundell,1 H Davis,3 A Armstrong,4 and N Thorp5.

1 Liverpool Reviews and Implementation Group (LRiG), University of Liverpool, Liverpool, UK
2 Department of Public Health Medicine, University of Liverpool, Liverpool, UK
3 North West Medicines Information Centre, Liverpool, UK
4 The Christie NHS Foundation Trust, Manchester, UK
5 Clatterbridge Centre for Oncology NHS Foundation Trust, Wirral, UK
* Corresponding author
Southampton (UK): NIHR Journals Library; 2011 Dec.
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Abstract

Background:

Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue affecting predominantly women. Metastatic breast cancer (mBC) is an advanced stage of the disease when the disease has spread beyond the original organ. Hormone receptor status and human epidermal growth factor 2 (HER2) status are two predictive factors that are taken into consideration when estimating the prognosis of patients with breast cancer.

Objectives:

To review the clinical effectiveness and cost-effectiveness evidence base for lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) mBC.

Data sources:

Relevant electronic databases and websites, including MEDLINE, EMBASE and the Cochrane Library, were searched until May 2010. Further data were derived from the manufacturers' submissions for LAP + AI and TRA + AI.

Review methods:

A systematic review of the clinical effectiveness and cost-effectiveness of LAP + AI and TRA + AI was undertaken. As it was deemed inappropriate to compare LAP + AI with TRA + AI, two separate assessments of cost-effectiveness versus AIs alone were undertaken.

Results:

Three trials were included in the systematic review [the patient populations of the efficacy and safety of lapatinib combined with letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with anastrozole (TAnDEM) trial and the efficacy and safety of letrozole combined with trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were believed to be inappropriate and meta-analysis was not possible. Individually, however, the findings from the trials all suggest that LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone. The trials do not show a statistically significant benefit in terms of overall survival. Two separate economic analyses were conducted based on the completed trials; neither LAP + AI nor TRA + AI was found to be cost-effective when compared with AI monotherapy.

Limitations:

Because of differences in the EGF30008 and the TAnDEM trials, the Assessment Group believes the indirect comparisons analyses conducted by the manufacturers are inappropriate and, for the same reason, chooses not to compare LAP + AI with TRA + AI in an economic evaluation.

Conclusions:

LAP + AI and TRA + AI appear to be clinically more effective than AI monotherapy, but neither is cost-effective compared with AIs alone. It was not possible to compare LAP + AI with TRA + AI. Future research should include research into treating mBC in the HR+/HER2+ population who are not TRA (or LAP) naive and into comparing the clinical effectiveness of AIs as monotherapy in patients with HER2+ and human epidermal growth factor 2-negative breast cancer.

Funding:

The National Institute for Health Research Technology Assessment programme.

Contents

Suggested citation:

Fleeman N, Bagust A, Boland A, Dickson R, Dundar R, Moonan M, et al. Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor-positive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis. Health Technol Assess 2011;15(42).

Declared competing interests of the authors: In the past, Anne Armstrong has received consultancy fees, reimbursement for attending a conference and hospitality at a conference, from Roche. The North West Medicines Information Centre, where Helen Davis is the Assistant Director, has received a consultancy fee from GlaxoSmithKline in the past for participation in a group discussing various mechanisms for managing NHS medicines budgets.

The research reported in this issue of the journal was commissioned and funded by the HTA programme on behalf of NICE as project number 09/101/01. The protocol was agreed in February 2010. The assessment report began editorial review in September 2010 and was accepted for publication in January 2011. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

© 2011, Crown Copyright.

Included under terms of UK Non-commercial Government License.

PMID: 22152751

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