Lapatinib for HER2 overexpressing breast cancer

This paper presents a summary of the evidencereview group (ERG) report into the clinicaleffectiveness and cost-effectiveness of lapatinib forthe treatment of advanced or metastatic HER2-overexpressing breast cancer based upon a reviewof the manufacturer’s submission to the NationalInstitute for Health and Clinical Excellence (NICE)as part of the single technology appraisal (STA)process. The scope included women with advanced,metastatic or recurrent HER2-overexpressingbreast cancer who have had previous therapy thatincludes trastuzumab. Outcomes were time toprogression, progression-free survival, responserates, overall survival, health-related qualityof life and adverse effects. The submission’sevidence came from one randomised controlledtrial (RCT) of reasonable methodologicalquality, although it was not powered to detect astatistically significant difference in mean overallsurvival. Median time to progression was longerin the lapatinib plus capecitabine arm than inthe capecitabine monotherapy arm {27.1 [95%confidence interval (CI) 17.4 to 49.4] versus 18.6[95% CI 9.1 to 36.9] weeks; hazard ratio 0.57 [95%CI 0.43 to 0.77; p = 0.00013]}. Median overallsurvival was very similar between the groups [67.7(95% CI 58.9 to 91.6) versus 66.6 (95% CI 49.1to 75.0) weeks; hazard ratio 0.78 (95% CI 0.55to 1.12; p = 0.177)]. Median progression-freesurvival was statistically significantly longer inthe lapatinib plus capecitabine group than in thecapecitabine monotherapy group [27.1 (95% CI24.1 to 36.9) versus 17.6 (95% CI 13.3 to 20.1)weeks; hazard ratio 0.55 (95% CI 0.41 to 0.74);p = 0.000033]. The manufacturer’s economicmodel to estimate progression-free and overallHTA 07/10/01Date of ERG submission:June 2007TAR Centre(s):Southampton Health Technology Assessments CentreList of authors:J Jones, A Takeda, J Picot, C von Keyserlingk and A CleggContact details:Andrea Takeda, Southampton Health TechnologyAssessments Centre, Wessex Institute for HealthResearch and Development, University of Southampton,Mailpoint 728, Boldrewood, Southampton SO16 7PX,UKE-mail: A.L.Takeda@soton.ac.ukThe research reported in this article of the journalsupplement was commissioned and funded by theHTA programme on behalf of NICE as project number07/10/01. The assessment report began editorial reviewin May 2008 and was accepted for publication in May2009. See the HTA programme web site for furtherproject information (www.hta.ac.uk). This summaryof the ERG report was compiled after the AppraisalCommittee’s review.The views and opinions expressed therein are those ofthe authors and do not necessarily reflect those of theDepartment of Health.Discussion of ERG reports is invited. Visit the HTAwebsite correspondence forum (www.hta.ac.uk/correspond).Lapatinib for the treatment of HER2-overexpressing breast cancer2survival for patients with HER2-positive advanced/metastatic breast cancer who had relapsedfollowing treatment with an anthracycline, a taxaneand trastuzumab was appropriate for the diseasearea. The base-case incremental cost-effectivenessratios (ICERs) for lapatinib plus capecitabinecompared with capecitabine monotherapy orvinorelbine monotherapy were higher than wouldconventionally be considered cost-effective.When compared with trastuzumab-containingregimes, lapatinib plus capecitabine dominated.In sensitivity analyses the ICER for lapatinibplus capecitabine compared with capecitabinemonotherapy or vinorelbine monotherapy wasrobust to variation in assumptions. In all sensitivityanalyses the ICERs remained higher than wouldconventionally be considered cost-effective.ICERs for trastuzumab-containing regimes wereparticularly sensitive to assumptions over thefrequency of treatment, which had a large effect onthe cost-effectiveness of lapatinib plus capecitabine.In conclusion, there was a general lack of evidenceon the effectiveness of comparators included inthe model and on key parameters such as doseadjustments and the model outputs need to beinterpreted in the light of this uncertainty. At thetime of writing, NICE were still considering theavailable evidence for this appraisal