|Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe
|Walleser S, Ray J, Bischoff H, Vergnenegre A, Rosery H, Chouaid C, Heigener D, Carpeno JC, Tiseo M, Walzer S
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
The cost-effectiveness of first-line maintenance erlotinib was compared with best supportive care in five European countries (UK, Germany, France, Spain and Italy) in patients with locally advanced or metastatic non-small cell lung cancer. The authors concluded that first-line erlotinib provided value-for-money compared with best supportive care irrespective of the country setting. The analysis used a valid methodology that reported data sources and considered key areas of uncertainty. The authors’ conclusions appear robust.
Type of economic evaluation
The cost-effectiveness of first-line maintenance erlotinib was compared with best supportive care in patients with epidermal growth factor receptor wild-type locally advanced or metastatic non-small cell lung cancer in five European countries (UK, Germany, France, Spain and Italy).
Erlotinib (150mg/day orally) plus best supportive care was compared with best supportive care alone. Docetaxel (for 90 days) was assumed to be used as second-line treatment in patients with disease progression after first-line treatment.
UK, Germany, France, Spain, and Italy/secondary care.
The analysis was based on a Markov model that used an area-under-the-curve approach with a lifetime horizon. The authors stated that the analysis took the perspective of the national health care payer.
Key clinical inputs for the model were taken from a multi-centre randomised placebo-controlled phase III trial (SATURN: Cappuzzo, et al. 2010, see 'Other Publications of Related Interest' below for bibliographic details). The trial enrolled 889 patients with locally advanced or metastatic non-small cell lung cancer after four cycles of platinum-based chemotherapy who received either erlotinib or best supportive care. Log-logistic functions were used to extrapolate short-term data from the trial to patients’ lifetime. Rates of progression-free survival and overall survival were the primary endpoints of the clinical analysis. Treatment effect for docetaxel was also taken from clinical trials.
Monetary benefit and utility valuations:
Measure of benefit:
Life years were used as the summary benefit measure and were discounted at an annual rate of 3.5%.
The costs of erlotinib and second-line treatment with docetaxel were included. Quantities of resources used mainly came from the SATURN trial. Drug costs were calculated on the basis of current ex-factory prices in each country. The analysis also considered the costs of treating erlotinib-related adverse events. Other costs were based on official listing prices or expert opinions. Costs were presented in Euros (EUR). UK £ were converted into Euros using the official exchange rate in 2010. A 3.5% annual discount rate was applied. The price year appears to have been 2010.
Analysis of uncertainty:
Both deterministic and probabilistic sensitivity analyses were carried out to investigate the impact of changes in key input parameters. One-way sensitivity analyses focused on the costs of drug administration, second-line treatment costs, discount rates for effects and costs, and treatment duration of erlotinib. The probabilistic sensitivity analysis was based on a second-order Monte Carlo simulation with 1,000 iterations and conventional distributions for groups of inputs.
For erlotinib, the mean lifetime life years were 1.49; for best supportive care, life years were 1.10.
The mean total cost of erlotinib was EUR 10,551 in the UK, EUR 13,203 in Germany, EUR 12,109 in France, EUR 11,039 in Spain, and EUR 10,542 in Italy.
The mean total cost of best supportive care was EUR 2,653 in the UK, EUR 3,623 in Germany, EUR 3,236 in France, EUR 2,551 in Spain, and EUR 2,393 in Italy.
The incremental cost per life year gained with erlotinib over best supportive care was EUR 20,711 in the UK, EUR 25,124 in Germany, EUR 23,271 in France, EUR 22,261 in Spain, and EUR 21,368 in Italy. All these ratios are well within the conventional cost-effectiveness thresholds.
No substantial variations in cost-effectiveness ratios were observed in the deterministic sensitivity analyses. The most influential inputs were discount rate and duration of treatment.
At a threshold of EUR 50,000 per life gained, the probability that erlotinib was cost-effective was 93.6% in the UK, 91.0% in Germany, 91.7% in France, 92.1% in Spain, and 92.9% in Italy.
The authors concluded that first-line erlotinib provided value-for-money compared with best supportive care for patients with advanced non-small cell lung cancer, irrespective of the country setting.
The selection of the comparators appropriately reflected the treatments available in the SATURN trial. The authors stated that pemetrexed was an alternative first-line option, which has been shown to be similarly effective and more costly than erlotinib.
Treatment effect and safety data for erlotinib versus best supportive care were obtained from a phase III, head-to-head clinical trial (SATURN) that included a large sample of patients; this should have provided valid estimates. The authors stated that a log-logistic function best fitted the estimates and was appropriately used to extrapolate longer term data. Sensitivity analyses were conducted on all model parameters.
Life years were a valid benefit measure given that survival was the most relevant outcome for patients with advanced non-small cell lung cancer. No attempt to include quality of life was made; it was unclear whether this would have had an impact on model results given the adverse events associated with erlotinib.
The analysis was consistent with the perspective adopted for each country. Official tariffs were used for most costs, although these estimates were supplemented by expert opinions. Resource use was mainly taken from the clinical trial; it appeared that pooled estimates were used. It was unclear whether these were representative of clinical practice in all the five countries. Unit costs were reported separately from quantities of resources used for some items. The price year was implicitly stated, which allowed reflation exercises in other time periods. Variations in economic inputs were appropriately considered in the sensitivity analyses.
Analysis and results:
An incremental approach was used to combine costs and benefits of the two treatments. Uncertainty was investigated using appropriate instruments with the methods and key findings clearly presented and discussed. Conventional discounting was applied but variations in discount rates were considered. Details of the model and the functions used to extrapolate the data beyond the trial period were presented. The results for each country were clearly reported. The analysis was conducted in five European countries finding similar results, so it is likely to be valid in other developed countries with similar drug prices.
The analysis used a valid methodology that reported data sources and considered key areas of uncertainty. The authors’ conclusions appear robust.
Walleser S, Ray J, Bischoff H, Vergnenegre A, Rosery H, Chouaid C, Heigener D, Carpeno JC, Tiseo M, Walzer S. Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe. ClinicoEconomics and Outcomes Research 2012; 4(1): 269-275
Other publications of related interest
Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G, SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncology 2010;11(6):521–529.
Subject indexing assigned by CRD
Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Europe; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Quinazolines
Date bibliographic record published
Date abstract record published