A study published in JAMA Oncology found that 31 genome-targeted anticancer agents were in use as of January 2018.1 To shed light on the current state of precision oncology, The ASCO Post recently spoke with David M. Cutler, PhD, the Otto Eckstein Professor of Applied Economics in the Department of Economics and Kennedy School of Government at Harvard University and Commissioner of the Massachusetts Health Policy Commission. Professor Cutler served on the Council of Economic Advisers and the National Economic Council during the Clinton Administration and advised the presidential campaigns of Bill Bradley and John Kerry. He also served as Senior Health Care Advisor for the presidential campaign of Barack Obama.
David M. Cutler, PhD
What’s in a Name?
Precision medicine is a widely used term. Please describe this term in the context of the oncology sector.
By definition, precision medicine is molecular profiling of tumors to identify alterations or other characteristics that can be targeted by a specially designed agent. Or, more broadly, precision oncology can be seen as matching specific patient groups to specific therapies that they may be more likely to respond to. Precision oncology is also used to describe the way clinicians select therapies based on data from the analysis of biomarkers. One important aspect of personalized oncology is that the prescribing of anticancer drugs is, more often than not, limited to the indication for which the drug was approved, unlike earlier developed therapies, which are commonly used off-label.
Please give the readers a sense of the therapeutic landscape in oncology precision medicine, in terms of its use and clinical outcomes.
For one, most of the oncologic agents coming down the pipeline into the U.S. Food and Drug Administration (FDA) approval process can be classified as having at least one component of what we call precision oncology, in that they apply genomics and other molecular analyses of tumor biopsies to improve diagnosis and treatment. We’re also seeing this play out in the design of clinical trials looking at biomarkers as endpoints.
We’ve seen some remarkable successes coming out of precision oncology, such as with imatinib, which has a 95% response rate in patients with chronic myeloid leukemia, extending quality-adjusted life by about 9 years. Then there’s venetoclax, which has shown an 80% response rate in patients with chronic lymphocytic leukemia who have a 17p deletion. So, we’re seeing the promise of this approach having real clinical benefits in some applications.
In theory, precision oncology offers a better way forward in the treatment of cancers across multiple sites; however, the overall clinical effect of precision medicine for patients with cancer has not been what we’ve hoped for. Even in those patients with cancer who have a clinically meaningful response from targeted agents, survival advantages are often measured in months. That said, I remain optimistic about precision oncology’s way forward, as our knowledge of cancer cell biology and molecular abnormalities increases.
Cost of Value-Based Care
Please discuss precision therapies in the cost equation of value-based care, also touching on Memorial Sloan Kettering Cancer Center’s “drug abacus.”
The cost of precision medicine is high, because treatments are expensive to develop and produce. But what we do know at this point is that for the very expensive precision oncology drugs that work well, such as imatinib, the cost-effectiveness to the health-care system adds value. The problem is that many of the precision oncology drugs coming onto the market do not extend survival enough to warrant their pricing.
A better metric than total spending is cost-effectiveness. Memorial Sloan-Kettering Cancer Center uses a “drug abacus” to determine whether the benefits of the drugs outweigh the costs. It evaluated 52 anticancer agents approved between 2001 and 2013 and estimated that a relative few were worth the extended quality-of-life valuations they offered patients with cancer.
Balancing Cost and Innovation
Is there a way to mitigate the rise in prices for the new era of precision drugs without stifling innovation?
To begin, although many of the new precision oncology drugs we’ve discussed are expensive, it’s important to note that total inflation-adjusted spending on anticancer drugs over the past decade or so has been fairly modest, making up just 6% or so of the total increase in personal health-care spending. Administrative costs, on the other hand, have risen about four times the amount spent on cancer drugs. Competition is probably the easiest way to reduce drug costs, and that can be done, in part, by accelerating the review time for new, competing agents onto the market. Finding ways to get more biosimilars to clinicians is another way.
Please share any closing thoughts on our biomedical innovation system: Are you optimistic or cautionary?
I’m very optimistic because of the incredible expansion of scientific knowledge we are gaining about the genomic and molecular complexities of cancer. I think it will roll out in stages, and we’re sort of at the end of stage one, which is the advent of precision medicine. We’ve seen that applying precision oncology to the clinic has proved to be challenging, producing some remarkable successes but far too many drugs that do not deliver enough benefit. It’s a building process, and we’re on the right track.
Along with biomedical advances comes a responsibility to the health of the whole system, so we need to employ proven measures to hold costs down by paying for drugs according to the value they offer patients with cancer. The outcome of how this is handled is immensely important to our society.
DISCLOSURE: Professor Cutler reported no conflicts of interest.
1. Marquart J, Chen EY, Prasad V: Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology. JAMA Oncol 4:1093-1098, 2018.