The cost of cancer drugs in the US: why we must look beyond published data

Tito Fojo1

1Columbia University Medical Center, New York, USA


Viewed by many as the system to emulate, our approach to cancer patients in the US is, like that of any other country, far from perfect. Many argue that the system is not sustainable and it is increasingly obvious that this is so. Included amongst the reasons for this problem is the high cost of pharmaceuticals, including those developed to treat cancer. A majority of approved cancer drugs are available to a majority of patients with cancer – often “off-label” – and one can say with confidence this will not change appreciably as it represents “the American way”. It is therefore incumbent on oncologists to ensure our decisions are evidence-based and that the evidence is sound. In this regard I would argue we have to consider several factors: [1] Clinical trial results are the best one can possibly achieve. Numerous examples have shown that once a drug has been approved outcomes in the community are inferior. This is often attributed to the use of agents in patient populations who are less fit and in patients who have already had multiple lines of therapy. The inferior outcomes obtained after drug approval makes estimates of cost/benefit somewhat misleading, given that such calculations are a best-case estimate and fail to account for results obtained once drugs enter the community setting. [2] Clinical trial results apply only to the setting in which they were conducted. One cannot extrapolate to other settings. Particularly, clinical trial results cannot be expected to be the same or even similar with more advanced disease or after other therapies have been received. [3] Increasingly marginal results that achieve statistical significance with large numbers of patients are of concern. The push to accept endpoints other than overall survival is problematic because outcomes such as progression-free survival can be greatly influenced by the extent of censoring, emerging as an increasing problem in oncology trials. [4] In a clinical trial not everyone achieves the median benefit. Especially with marginal results, only a small percentage of patients achieve meaningful benefit and others are actually harmed. One can expect that the more marginal the results the greater the fraction of patients that are harmed. [5] Harm from a therapy can take many forms but most often is manifested as physical toxicity. In the era of targeted therapy, such toxicity can be a major problem because these agents are administered daily. This assumes special importance because such toxicity is usually managed by dose reductions and this invariably means reduced efficacy. While cancer patients looking for hope in a therapy often voice the sentiment that nothing can be worse than the death they feel is a certainty, seasoned oncologists know there is something far worse – death from cancer complicated by the toxicity of a treatment that brought no benefit. The US system is unlikely to change or adapt a rational approach such as that employed by NICE. Its hope lies in oncologists, especially academic oncologists, ensuring our therapies bring more than marginal benefits, are based on studies applicable in the community and are as free of toxicity as possible.