In a Belgian study published (Wednesday 30 November) in Annals of Oncology, health economist Mattias Neyt said that if the drug turns out to be as powerful in early breast cancer as preliminary results show, then it may well be cost effective for certain sub-groups.
However, using it as adjuvant therapy in early disease could impose a major financial burden on healthcare systems because of the high drug price, the long duration of treatment and the large numbers of women who would be eligible. If patients are not to be denied the treatment, healthcare authorities will have to bargain over the drug price and be prepared to reallocate resources and de-list older non-cost effective treatments in order to meet the demand.
Mr Neyt, a research fellow at Ghent University, said: "In Belgium there are over 6,600 cases of breast cancer a year. About 45% are stage II or III - the first sub-groups in which adjuvant therapy would probably be used - and about a quarter of these would have the type of breast cancer that responds to Herceptin. This means that about 750 women each year would be eligible. The cost of providing the treatment in Belgium would be 25.5 million Euro or around 34,000 Euro per patient for Herceptin drug costs alone. Extending its use to stage I breast cancers would double the burden.
He said these costs could be even higher in some countries because the price of the drug varies widely. For example, in Norway, at current prices, Herceptin is 928 Euro per 150mg vial, compared with 647 Euro per vial in Belgium. In the UK, the price to the National Health Service is about 595 Euro.
Herceptin (trastuzumab) is a humanised monoclonal antibody that targets those breast cancers expressing a protein called HER2 - around a quarter of all breast cancers. It is currently licensed for use in advanced (metastatic) breast cancer where it has been shown to extend survival. Four trials of its use in early breast cancer are underway and preliminary results are promising.
The drug is the cause of controversy in many countries because of pressures from some quarters, including patients, for it to be made available immediately for early breast cancer, without waiting for the outcome of these trials.
Mr Neyt and his colleagues at Ghent University and University Hospital Ghent, carried out their economic evaluation of adjuvant Herceptin based on a group of patients aged over 50 with stage III breast cancer (locally advanced node positive). Patients received Herceptin treatment in one of the trials - the Breast Cancer International Research Group (BCIRG 006) trial, which involves Belgian hospitals, including Ghent. Ghent hospital's budget parameters were used as a benchmark for a complex series of calculations comparing the new treatment with a standard treatment in a setting that took into account all the phases from diagnosis through to after-care and also included the possible advantage of Herceptin in reducing the percentage of cancers that became metastatic. However, it did not take into account societal costs e.g. those involved in loss of work time, travelling and so on.
How much society is willing to pay for health improvements is uncertain, Mr Neyt said. Some studies suggested that in the USA it is at least $100,000 (approx. 85,000 Euro) per quality adjusted life year (QALY) and even recommended it should be double that figure. In the UK the implicit threshold is about £30,000 (approx. 48,000 Euro). For the study, the threshold was set at 50,000 Euro.
"We must wait for future trial results to confirm the promising preliminary results. Nevertheless, in comparison with the metastatic setting, the potential of Herceptin and the health gains are greater in the adjuvant setting. Response usually improves when drugs are used earlier in the disease and when looking at the higher costs involved, we should not forget that adjuvant treatment is curative in the first place. If more people are cured, expensive future costs for treating metastatic cancer are avoided."
But, he warned that, depending on the willingness to pay for health improvements, there would have to be tough bargaining over the drug's price to reach acceptable extra costs for the health gains. "Even after the company has set its price at a level acceptable to them and which produces acceptable incremental cost-effectiveness ratios, it is still possible that present budgets will not be able to bear the extra expense.
"This means countries should not rush into prescribing it before working out the implications very carefully and being prepared to reallocate resources, get rid of other treatments that are no longer cost-effective and drive a hard bargain over the price of the drug.
"When it comes to price-bargaining, governments want to spend their money well and maximise health gains. The pharmaceutical company wants its product to be reimbursed for a large population in order to sell large volumes. So, the aim is to arrive at a price that results in cost effective treatment, which budgets can bear, even if the drug is provided for a large number of women. This is the only way to reach a win-win situation for everyone - government, company and most of all, patients."
Mr Neyt added: "The Lancet recently stated that it was vital that the decisions made by drug regulatory agencies such as the UK's National Institute of Clinical Excellence (NICE) are made carefully after considering all available evidence and should be free from political, special interest or media influence no matter how well-meaning. We face the same situation in Belgium where the Belgian Health Care Knowledge Centre will be evaluating Herceptin."
 An economic evaluation of Herceptin® in adjuvant setting: the Breast Cancer International Research Group 006 Trial. Annals of Oncology. doi.101093/annonc/mdj101.
 Quality life adjusted year (QALY): the arithmetic product of life expectancy and a measure of the quality of the remaining life years, which places a weight on time in different health states, with perfect health being 1 and a year of less than perfect health life expectancy being less than 1.
 The Lancet, November 12, 2005, p1673.
A PDF of the research paper is available on request.
Please acknowledge Annals of Oncology as a source in any reports.
Annals of Oncology is the monthly journal of the European Society for Medical Oncology.
Annals of Oncology website: http://annonc.