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Cost-effectiveness analysis of anastrozole vs tamoxifen in adjuvant therapy for early stage breast cancer in the United Kingdom: the 5-year completed treatment analysis of the ATAC ('Arimidex', Tamoxifen alone or in combination) trial.

ABSTRACT: Results from the completed treatment analysis of the ATAC (Arimidex, Tamoxifen alone or in combination) trial indicated that anastrozole was significantly superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal women with hormone receptor-positive (HR+) early breast cancer. On the basis of these results, this study estimated the cost-effectiveness of anastrozole vs tamoxifen, from the perspective of the UK National Health Service (NHS). A Markov model was developed using the 5-year completed treatment analysis from the ATAC trial (ISRCTN18233230), as well as data obtained from published literature and expert opinion. Resource utilisation data and associated costs (2003-4 UK pound) were compiled from standard sources and expert opinion. Utility scores for a number of health states were obtained from a cross-sectional study of 26 representative patients using the standard gamble technique. The utility scores were then inserted into the model to obtain cost per quality adjusted life-year (QALY) gained. Costs and benefits were discounted at recommended annual rates of the UK Treasury (3.5%). Modelled for 25 years, anastrozole, relative to generic tamoxifen, was estimated to result in 0.244 QALYs gained per patient at an additional cost of pound4315 per patient). The estimated incremental cost-effectiveness of anastrozole compared with tamoxifen was pound17 656 per QALY gained. There was a greater than 90% probability that the cost-effectiveness of anastrozole was below pound30 000 per QALY gained and of the order of 65% that it was below pound20 000 per QALY gained. The results were robust to all parameters tested in sensitivity analysis. Compared with commonly accepted thresholds, anastrozole is a cost-effective alternative to generic tamoxifen in adjuvant treatment of postmenopausal women with HR+ early breast cancer from the UK NHS perspective.

SUBMITTER: Mansel R

PROVIDER: S-EPMC2360294 | biostudies-other | 2007 Jul

REPOSITORIES: biostudies-other

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Project description:Purpose:To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2-3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years. Patients and methods:Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ?4 cm breast cancer patients who had received tamoxifen for 2-3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2-3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events. Results:A total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3-4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group. Conclusion:For early-stage breast cancer patients who remain premenopausal following 2-3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment. Trial Registration:ClinicalTrials.gov (identifier NCT01352091).

Project description:IntroductionTamoxifen is one of the most effective adjuvant breast cancer therapies available. Its metabolism involves the phase I enzyme, cytochrome P4502D6 (CYP2D6), encoded by the highly polymorphic CYP2D6 gene. CYP2D6 variants resulting in poor metabolism of tamoxifen are hypothesised to reduce its efficacy. An FDA-approved pre-treatment CYP2D6 gene testing assay is available. However, evidence from published studies evaluating CYP2D6 variants as predictive factors of tamoxifen efficacy and clinical outcome are conflicting, querying the clinical utility of CYP2D6 testing. We investigated the association of CYP2D6 variants with breast cancer specific survival (BCSS) in breast cancer patients receiving tamoxifen.MethodsThis was a population based case-cohort study. We genotyped known functional variants (n = 7; minor allele frequency (MAF) > 0.01) and single nucleotide polymorphisms (SNPs) (n = 5; MAF > 0.05) tagging all known common variants (tagSNPs), in CYP2D6 in 6640 DNA samples from patients with invasive breast cancer from SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity); 3155 cases had received tamoxifen therapy. There were 312 deaths from breast cancer, in the tamoxifen treated patients, with over 18000 years of cumulative follow-up. The association between genotype and BCSS was evaluated using Cox proportional hazards regression analysis.ResultsIn tamoxifen treated patients, there was weak evidence that the poor-metaboliser variant, CYP2D6*6 (MAF = 0.01), was associated with decreased BCSS (P = 0.02; HR = 1.95; 95% CI = 1.12-3.40). No other variants, including CYP2D6*4 (MAF = 0.20), previously reported to be associated with poorer clinical outcomes, were associated with differences in BCSS, in either the tamoxifen or non-tamoxifen groups.ConclusionsCYP2D6*6 may affect BCSS in tamoxifen-treated patients. However, the absence of an association with survival in more frequent variants, including CYP2D6*4, questions the validity of the reported association between CYP2D6 genotype and treatment response in breast cancer. Until larger, prospective studies confirming any associations are available, routine CYP2D6 genetic testing should not be used in the clinical setting.

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Cost-effectiveness analysis of anastrozole vs tamoxifen in adjuvant therapy for early stage breast cancer in the United Kingdom: the 5-year completed treatment analysis of the ATAC ('Arimidex', Tamoxifen alone or in combination) trial.

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