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Reflections on the value of new cancer drugs: The role of the man in the mirror
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I’m starting with the man in the mirror
I’m asking him to change his ways
— Michael Jackson
The cost of cancer drugs has been the subject of intense interest and scrutiny.
This is no surprise as the focus on value in cancer care increases, because cancer drugs represent easily identifiable low-hanging fruit to reduce the cost component of the value equation.
The cost of new anticancer drugs is increasing at an alarming rate. We have reached the point at which 1 year of therapy with a combination immunotherapy regimen costs more than the median price of a home in the United States. Clearly, this is not sustainable.
Shift toward academia
Much has been written about the spiraling costs of these drugs, and most lay the responsibility firmly on the pharmaceutical industry. The industry has defended its record mainly based on the high costs associated with drug development — in particular, large registration trials of their products. Although this debate has occurred in the literature and at meetings, not much has happened to address the issue.
A very thoughtful commentary published in Cell provided an overview of the problem and a potential solution that involves a new model of academic–commercial partnerships. The article cited the examples of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center and The Cancer Research UK Cancer Therapeutics Unit in London as large-scale drug discovery facilities based in academic centers that have the capacity for drug development previously only available to industry.
These organizations still have challenges. Most do not have the resources to run large-scale registration trials, but with the increasing emergence of targeted therapies, biomarker-driven trials are reducing the need for such studies. Similarly, commercialization of new drugs may not be a strength of academic entities, but academic–private partnerships could play a major role in this area.
So, there is hope that a gradual shift in the drug development world toward academic centers with different incentives from the pharmaceutical industry might eventually help curtail costs. This, however, will take time and raises the question of what can be done in the meantime.
Further, the drug development process is only part of the problem. Changes in FDA approval may have further fueled the rapid rise in costs, which has been exacerbated by a failure to monitor postmarketing studies of many approved agents.
Drug approval
And then there’s us. As prescribing oncologists, we should think about our role in controlling these costs.
We have witnessed the introduction of some practice-changing drugs in the past couple years. Perhaps the best examples are checkpoint inhibitors and other immune therapies, which ASCO again cited as its advance of the year.
In contrast, many other new and expensive drugs have been introduced with surrogate efficacy endpoints and very marginal — if any — benefit.
The definition of benefit in this context is, of course, open to interpretation. In 2014, ASCO published definitions for clinically meaningful outcomes in clinical trials, which — for various metastatic solid tumors — were identified as improvements in median OS of between 2.5 and 6 months. The society also made recommendations for improvements in PFS.
These criteria were chosen partly to recognize that — even at a time of emergence of new, targeted therapies — improvements are likely to be small and incremental, and relatively small improvements can be meaningful. These criteria do not factor in patient-reported outcomes, quality of life, cost and other important metrics, but new value frameworks are emerging as tools to evaluate the true benefit of drugs.
These tools can’t come soon enough. One report used ASCO recommendations to compare 47 cancer therapies the FDA approved from April 2014 to February 2016. Of these therapies, 10 received accelerated approval based on single-arm trials and, therefore, cannot be judged against the ASCO benchmark. Of the remaining 37 therapies, 25 met standards for PFS but only nine met standards for OS.
Another study examined 36 drugs the FDA approved based on surrogate endpoints — response rate, PFS or DFS — between 2008 and 2012. Only five improved OS in subsequent studies. For many others, the effect on OS is unknown, suggesting the FDA approves too many expensive therapies and that postmarketing surveillance of these drugs is inadequate.
The price of many new cancer drugs apparently correlates poorly with their efficacy.
The FDA approved 51 cancer drugs between 2009 and 2013. Of these, 21 exploited a novel mechanism of action, whereas 30 were next-in-class (“me too”) drugs. The price per year of therapy was the same for both classes ($119,765 vs. $116,100).
Drugs approved based on response rate only were the most expensive, at $137,952 per year, compared with $102,677 for drugs approved based on OS benefit. No correlation existed between cost and PFS or OS improvements.
Although the effects of newly approved drugs on quality of life have been sparse, one study analyzed 18 cancer drugs approved by the FDA that were not shown to improve OS in subsequent postmarketing studies. Quality-of-life studies were available for seven of these drugs, six of which had no effect on quality of life. These drugs cost an average of $87,922 per year, and all but one still have FDA approval.
‘Man in the mirror’
What can we conclude from this?
The cause of high drug costs is multifactorial. In addition to the prices set by industry, the FDA’s understandable need to have potentially active drugs approved quickly based on “soft” endpoints, as well as the lack of adequate patient-reported outcomes and the apparent failure of postmarketing surveillance, are all contributors.
Some countries have addressed this problem by setting a high bar for cancer drug approval and funding. The National Institute for Health and Care Excellence in the United Kingdom has succeeded in limiting costs, but only by severe limitation of or delay in approval of some expensive therapies.
While we wait for better value-assessment tools and for a more rigorous approach to postmarketing studies, we need to remember that we are part of the drug-cost problem and should be part of the solution. We, as oncologists, are prescribing these drugs, many of which we know to have marginal benefit but huge financial toxicity for our patients.
If we are circumspect about our use of these agents, in the context of the well-published efficacy and cost data, we might be able to reduce the number of prescriptions issued for these therapies. I suspect this would be the first step in moving prices downward. Even if this approach has no effect on cost, it may benefit patients by avoiding unnecessary toxicity.
As we look toward a solution to the escalating cost of anticancer drugs, we should remember Michael Jackson’s words, and take a look toward the man in the mirror.
References:
ASCO. Clinical Cancer Advances 2017. Available at: www.asco.org/research-progress/reports-studies/clinical-cancer-advances. Accessed on Feb. 15, 2017.
Ellis LM, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2013.53.8009.
Kim C and Prasad V. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2015.5868.
Kumar H, et al. JAMA Oncol. 2016;doi:10.1001/jamaoncol.2016.0931.
Mailankody S and Prasad V. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.1959.
Rupp T and Zuckerman D. JAMA Intern Med. 2017;doi:10.1001/jamainternmed.2016.776.
Workman P, et al. Cell. 2017;doi:10.1016/j.cell.2017.01.034.
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John Sweetenham, MD, FRCP, FACP, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director of Huntsman Cancer Institute at University of Utah. He can be reached at john.sweetenham@hci.utah.edu.
Disclosure: Sweetenham reports no relevant financial disclosures.