Oncologists speak out

Media Release from Dr Richard Isaacs, Medical Oncologist, Palmerston North and ANZ Breast Cancer Trials Group, Chair Breast Cancer Special Interest Group of the New Zealand Association of Cancer Specialists and Associate Professor Fran Boyle, Medical Oncologist, University of Sydney and ANZ Breast Cancer Trials Group.

12 August 2008

The recent decision of PHARMAC not to fund 12 months of adjuvant Herceptin for women with Her 2 positive breast cancer calls into question our carefully crafted approach to ethical clinical trials research in cancer.  Since that decision there has also been much discussion in the media, questioning the rationale for 12 months of therapy and challenging this duration as the standard of care internationally. We would thus like to present our perspective as cancer therapists and researchers, not only to improve accuracy, but also to keep faith with our patients who are treated in this manner.

Large randomised trials and combined analyses have become the usual standard for new treatments to enter the clinic for common cancers. These trials receive extensive scrutiny from ethical and scientific perspectives before they begin and during their course, and the best studies are run by academic research groups which provide a further objective distance from the pharmaceutical industry. It is well designed trials such as this that hundreds of New Zealand women have participated in over the past decade. They are expensive to run, and add significantly to the cost of bringing new medicines to market, but give us the greatest confidence that the results are sound. It is the opinion of the research community that the large adjuvant Herceptin trials including 12 months of therapy fulfil these criteria of excellence.

The much smaller FINHER study which used 9 weeks of Herceptin is also of interest, but due to its small size should be regarded as a reason to proceed to a definitive study, not as immediate proof of equal effectiveness to the 12 month studies.

Because of their size and rigor, the 12 month trials have shown major gains in the treatment of Her2 positive breast cancer, which are yet to be established for a 9 week therapy. In particular these include:

1. Confidence in trial results. The 12 month trials included >11,000 patients, while the 9 week FinHer trial, on which PHARMAC base their funding, had only 232 patients. This gives much greater certainty with results from the 12 month trials.

2. Clear evidence of lives saved by therapy. The 12 month trials now all show an overall survival benefit - less women will die from this form of breast cancer when treated in this way. The risk of dying with 12 months therapy is reduced by about 1/3 at any stage after therapy.  In New Zealand the current data indicates we would save the lives of 12 women after 2 years and the cumulative number of lives saved will continue to increase with time. It takes time and study size to show these benefits, which the 9 week trial was too small to confidently show.

Cardiac safety has been highlighted as a concern. Indeed, up to 4 out 100 women developed reversible heart failure related to Herceptin in the 12 month trials compared to none in the 9 week. However, this is likely to be another effect of trial size – since 9 week funding was introduced heart failure has also occurred with that regimen, indicating we can not have faith in its absolute safety.

Treatment cost has been another major area of discussion, although PHARMAC stated their decision was based on the science not the cost.  All countries will need to make decisions on health care costs based on setting thresholds for both cost effectiveness (the extra cost of saving each life) and total cost (the total number of people who might need treatment) and competing health priorities. New therapies are not all of equal importance and impact and not all will make major differences to the health of nations. Herceptin when given for 12 months has shown major impacts on breast cancer relapse and survival, while the expected costs have certainly been overstated in recent days. Transparency of the decision-making process will allow resources to be allocated in ways that increase public trust.

What is vital is to keep separate the debates about the quality of the science and its ethical constraints, from decisions about how much nations want to spend. Confusing the two is of no benefit to the public, to women with breast cancer and to the volunteers, both patients and clinicians, who have laboured to bring this knowledge to light.