This study examined the cost-effectiveness of letrozole, tamoxifen, and anastrozole as additional treatment for patients with hormone receptor-positive breast cancer. It assessed the expiry of the patent for anastrozole and the future expiry of the patent for letrozole. The authors concluded that letrozole was cost-effective. This economic evaluation followed conventional cost-effectiveness guidelines and was satisfactorily presented. The authors’ conclusions appear to be robust.

Cost-effectiveness analysis, cost-utility analysis

This study examined the cost-effectiveness of letrozole, tamoxifen, and anastrozole as additional treatments for patients with hormone receptor-positive breast cancer. The analysis assessed the expiry of the patent for anastrozole and the future expiry of the patent for letrozole.

Two aromatase inhibitors, namely letrozole and anastrozole, were compared with tamoxifen. Each treatment was administered for five years.

Germany/secondary care.

Analytical approach:

The analysis used a Markov model, with a time horizon of 20 years. The authors stated that they took the perspective of the German health care system.

Effectiveness data:

The key evidence on survival for each of the three treatments was from various publications, including the Breast International Group (BIG) 1-98 study, the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study, and the Early Breast Cancer Trialists’ Group (EBCTG) study. These studies were clinical trials that included at least two of the three drugs. Baseline mortalities were based on the tamoxifen arm of the BIG 1-98 study and hazard ratios were applied for the other two treatments based on BIG 1-98 and ATAC study data. The EBCTG study was mainly used for long-term survival rates. Disease-free survival and recurrence rates were important inputs and were from these studies.

Monetary benefit and utility valuations:

The health utilities were from a sample of 600 patients, identified at the Department of Gynaecology in the Erlangen University Hospital, who completed a visual analogue scale (VAS). Where data were missing, published evaluations elicited using the standard gamble method, from American and British patients, were used.

Measure of benefit:

Quality-adjusted life-years (QALYs) and life-years were the summary benefit measures and they were discounted at an annual rate of 3%.

Cost data:

The analysis included the costs of the drugs, as well as care, diagnosis, and treatment for patients with hormone receptor-positive breast cancer. In-patient and out-patient services were considered and the incidence of adverse events was assessed. The costs were estimated from official German sources, while the patterns of resource consumption were based on guidelines, published studies, or expert opinion. All costs were in Euros (EUR). A 3% annual discount rate was applied and the price year was 2010.

Analysis of uncertainty:

Sensitivity analyses were carried out, using simple standard deviation, for the cost parameters, and published confidence intervals, for the clinical efficacy parameters. Probabilistic analysis was performed based on Monte Carlo simulation, with 2,000 scenarios. Different prices for anastrozole and letrozole after patent expiry (75%, 50%, and 25% of original prices) were considered.

In the base case (75% cost for anastrozole and 100% cost for letrozole), the total costs were EUR 16,308.10 with tamoxifen, EUR 25,484.12 with letrozole, and EUR 22,546.14 with anastrozole. The expected life-years were 12.4860 with tamoxifen, 12.7950 with letrozole, and 12.5300 with anastrozole, and the QALYs were 11.7267 with tamoxifen, 12.0391 with letrozole, and 11.7926 with anastrozole.

Compared with tamoxifen, the incremental cost per QALY gained was EUR 29,375.15 with letrozole and EUR 94,648.03 with anastrozole.

Reductions in the drug prices improved the cost-effectiveness of the two aromatase inhibitors. At 75% of its licensed price, the incremental cost per QALY for letrozole, compared with tamoxifen, fell to EUR 20,988.59, at 50% it was EUR 12,602.03, and at 25% it was EUR 4,215.46. The incremental cost per QALY for anastrozole was reduced substantially with reductions in drug prices; it was EUR 54,715.17 at 50% of licensed price and EUR 14,779.67 at 25%. In general, wide intervals around the mean cost-effectiveness values were found when the efficacy rate was varied within its 95% confidence interval.

The probabilistic sensitivity analysis showed similar results.

The authors concluded that letrozole was cost-effective for these patients.

Interventions:

The selection of the comparators was appropriate as commonly used treatments for patients with hormone receptor-positive breast cancer were considered.

Effectiveness/benefits:

The efficacy and safety data were from head-to-head clinical trials that should have had high internal validity. The long follow-up of these studies (up to nine years) provided valid data. The authors used appropriate methods to account for crossover between treatments (inverse probability censoring weighted analysis) and an intention-to-treat analysis was conducted. The sensitivity analysis showed the impact of the efficacy rates on the cost-effectiveness results. Both benefit measures were appropriate for capturing the impact of the treatments on the patients’ health. They were both comparable with the benefits of other health care interventions. QALYs were particularly relevant as the disease dramatically affects health-related quality-of-life. The authors pointed out that the use of German utility values was relevant for this analysis, but issues around the use of a VAS should be considered.

Costs:

The economic analysis was satisfactorily carried out and the costs were relevant to the perspective. Some of the unit costs were reported for drugs, but most of the data were presented as category totals. The data sources were appropriate for the German health care system. The analysis focused on the impact of future reductions in drug prices on the cost-effectiveness results and hypothetical reductions of 75%, 50% or 25% were considered. Reflation exercises are possible as the price year was reported. Conventional discounting was applied to the costs.

Analysis and results:

The results were clearly presented. The expected costs and benefits were appropriately synthesised, using an incremental approach. The uncertainty was investigated, using a probabilistic analysis, and by varying the costs of the drugs, which was the main focus of the analysis. The authors compared their results with those of other published studies which generally showed a good cost-effectiveness profile both for letrozole and anastrozole compared with tamoxifen. Some limitations of the analysis were acknowledged, such as the estimate of 100% compliance which was unlikely in the real world. The results were specific to Germany, but might be relevant to other locations, with similar drug prices.

Concluding remarks:

This economic evaluation followed conventional cost-effectiveness guidelines and was satisfactorily presented. The authors’ conclusions appear to be robust.

Support received from Novartis Oncology, manufacturer of letrozole.