No Easy Answers in Bioethics Podcast

Ethics and Policy Issues of Targeted Cancer Therapies: Fleck and Mackenzie – Episode 16

October 9, 2019 Leonard FleckStephanie Mackenzie photo

What kinds of challenges currently exist within precision medicine? This episode focuses specifically on targeted cancer therapies, featuring a discussion between Center Professor and Acting Director Dr. Len Fleck and College of Osteopathic Medicine student Stephanie Mackenzie. Dr. Fleck discusses ethics, economic, medical, and health policy issues related to these high-cost therapies. Additionally, he provides insight into how U.S. pricing models for these therapies compare with other countries.

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: "While We Walk (2004)" by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License.

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Episode Transcript

Liz McDaniel: Hello and welcome to another episode of No Easy Answers in Bioethics, the podcast from the Center for Ethics and Humanities in the Life Sciences at the Michigan State University College of Human Medicine. This episode focuses on targeted cancer therapies within precision medicine health care. College of Osteopathic Medicine student Stephanie Mackenzie speaks with Center Professor and Acting Director Dr. Len Fleck, who discusses ethics, economic, medical, and health policy issues related to these high-cost therapies. Additionally, Dr. Fleck provides insight into how U.S. pricing models for these therapies compare with other countries.

Len Fleck: Hello everybody, I'm Len Fleck. I'm a professor of philosophy and medical ethics and acting director in the Center for Ethics in the College of Human Medicine here at Michigan State University.

Stephanie Mackenzie: Hi, my name is Stephanie Mackenzie. I am a second-year medical student at Michigan State's College of Osteopathic Medicine.

LF: Today we're going to be talking about precision medicine. But we're going to be talking about precision medicine not so much as pure medicine, but rather, we want to look at some of the ethical and policy issues that are associated with precision medicine. When we say precision medicine, first of all my things we want to have in mind, we're talking about this in connection with so-called targeted cancer therapies, and we're talking about this in connection with patients who have advanced or metastatic cancer.

SM: So what exactly is precision medicine? Isn't that what used to be called personalized medicine.

LF: Yeah, it is what used to be called personalized medicine. And the basic idea behind—we'll start with personalized medicine—is that we, medicine needs to be more precise than it has been in the past. It needs to, in one way or another, address the medical problems of this very particular person. And so it's a reaction against what you might call "one size fits all" type of medicine. Instead of focusing on a broad problem, say stomach cancer, or lung cancer, or something like that, the idea is that what we've learned over the past several years, over the past couple decades, is that cancer is more correctly described in terms of its genetic mutations that are actually driving the cancer. And so the goal is to find particular drugs that attack the particular genetic features of a cancer. And in effect in that way getting beyond the idea that there is one size of a cancer drug that fits everybody who has lung cancer or everybody who has a stomach cancer or something like that. That's the basic idea.

SM: That sounds wonderful. Can we expect all patients with metastatic cancer to benefit from these advances?

LF: Well, the short answer to that question is no. There are medical reasons why that's the case, and there are cost-benefit or economic reasons why that's the case, and there are health insurance reasons why that the case, and there are political reasons why that's the case, and there are ethical reasons why that's the case.

SM: This all sounds very complicated. Can you tell me more about those medical reasons?

LF: Well the medical reasons have to do with, again as I was saying before, a lot of the research that has gone on with regard to cancer over the past couple decades. And one of the things that has been discovered that in the case of metastatic cancer, the cancer has usually evolved and become very genetically complex. It now has literally hundreds of mutations that are part of those cancer cells. This is what's sometimes referred to as intra-tumor and inter-tumor heterogeneity. Basically what that means is that unlike all the other cells in our body that are basically carbon copies of one another, or virtually carbon copies of one another, these cancer cells have distinct genetic features. It's typically the case that there is a particular genetic mutation that is identified as the driver of that cancer. And that driver might be what's called an EGFR mutation, or an ALK mutation, or HER2, H-E-R-2 mutation. But that's the genetic feature of the cancer that is going to be attacked by one of these particular cancer therapies.

The problem is that because these, these tumor cells are so heterogeneous and are evolving as we attack the cancer with these drugs, that we in fact are successful in finding a drug that will attack a cancer that is HER2 positive or that is ALK positive, and so for a brief period of time that cancer is held in check. But then there are other genetic mutations that, in a kind of Darwinian fashion, become the drivers of that cancer. And so then after a brief hiatus in which the cancer is held in check, the cancer again begins to grow this time driven by a different genetic characteristic of that cancer. The practical medical consequence of this is that the gains in life expectancy that can be expected from these drugs for the vast majority of patients will be measurable in months, not years. Again you need to keep in mind these are patients who have metastatic disease, these are not patients in the early stages of a cancer.

SM: This must have a substantial effect on our economy, can you tell us about the economic challenges?

LF: There are a considerable number of economic challenges. You might start with some basic statistics. In the United States about 610,000 individuals will die of cancer in a particular year, and 1.7 million individuals in any given year will be diagnosed with a cancer. Now those who are diagnosed with early cancer are oftentimes cured, so that's good. But otherwise for metastatic cancer, that is for the vast majority of patients, this is a terminal diagnosis. The basic economic problem is that there are very very high costs associated with these targeted cancer therapies, and the benefits are marginal. We say the benefits are marginal because, as I said before, the gains in life expectancy for the vast majority of patients will be measurable in months, not years. To be a little bit more precise, there are now about 90 of these FDA approved targeted cancer therapies. The cost of most of these drugs is at least $100,000 and sometimes it will be approaching $200,000 for a course of treatment or for one year's worth of treatment. So an example of what I have in mind here were would be a drug called osimertinib, the brand name is Tagrisso, and it's used to treat patients who have EGFR mutated non-small cell lung cancer. That drug costs a total of $186,000 per year. Now it is very beneficial in that the median gain in survival will be approximately 3 years. So that's much better than a lot of other of these targeted cancer therapies, but still that's a very very high cost.

The highest cost issue out there right now with regard to these cancer drugs has to do is a form of immunotherapy called CAR T-cell therapy. The cost of CAR T-cell therapy, which is an extremely complicated process in which T cells, the cells that attack cancer or that attack other kinds of diseases in your body, those T cells are in effect modified so that they can once again recognize and attack more effectively cancer cells. But the cost of doing CAR T-cell immunotherapy is $475,000. Unlike the targeted cancer therapies, CAR T-cell therapy has that $475,000 cost right at the front end. So no matter what the outcome is, you have to pay $475,000. Unlike a targeted therapy which would have a monthly cost of $12,000, $15,000 per month. And so there's a limit to the cost in that regard. What makes it more challenging from an economic point of view, as well as we'll see from a moral point of view, is that 30 percent of the patients who receive CAR T-cell therapy, mostly for blood cancers, will not survive more than a year. And so that looks like an awful lot of money to spend for less than a year's gain in life expectancy.

SM: Could you tell us a bit about how other countries compare with their health care expenditure? And the way that their economies runs with that?

LF: Well, of course this varies a lot from one place to another. So other countries in the world, most European countries, Canada for example, they have comprehensive health insurance that covers everybody in their society. And so if they approve a particular targeted cancer therapy for a particular kind of cancer, then it in fact will be available to everybody no matter what their own individual ability to pay might be. In the United States, however, we have an extraordinarily fragmented system for financing health care. So we have all these different health insurance plans with all kinds of co-pays and deductibles and what's covered and what's not covered and so on, along with Medicare and Medicaid and the Veterans Affairs system and so on. And so the net result of that is that individuals have radically different access to these extraordinarily expensive cancer therapies depending upon where they are in terms of the insurance pool. For many workers, roughly one-third of workers in the United States today, their health plans are or include a deductible of $5000. And so what that means is that those patients are responsible for paying the first $5000 worth of health care costs that they might incur. The practical consequence of that, for half of Americans, is that they, half of Americans have less than $500 in savings. And so a $5000 deductible right the front end of a very expensive therapy is something that's simply impossible for them to manage.

Also, as far as insurance is concerned, many insurance plans require co-pays for especially these kinds of drugs. These are referred to as Tier 4 drugs, so that's the uppermost tier in most health plans. And those Tier 4 drugs may require a co-pay of 20 percent or 30 percent. So if somebody needs that drug osimertinib that I mentioned before that as a cost of $186,000 for a year, even if they have a co-pay of only 20 percent, that represents approximately $40,000 that they would be responsible for each year that they need to be on that drug, and that that drug prolongs their life.

The other thing that insurance companies get concerned about is they want to know that there is in fact sound medical experimental scientific evidence for the effectiveness of these therapies. And they are not going to pay for what they regard as experimental interventions. The problem is that in many cases, what we regard as experimental is going to be true with many many individual patients. So even though the drug has been approved as having some effectiveness for many patients with this particular cancer, nevertheless there may be genetic features of an individual that make it very uncertain as to whether or not this drug is going to do very much good for them. So to give you a quick example, patients who have what's called HER2, H-E-R-2 metastatic breast cancer would typically be treated with a drug called trastuzumab or Herceptin is the brand name. The problem is that we think of, we're inclined to think that you either have tumors that are HER2 positive or they're not HER2 positive. Like it's, there's a sharp division there. But that's not the medical or biological reality. The reality is that there's a kind of continuum along the way, and so there are degrees of being HER2 positive. And so in some sense, the stronger it is the case that you are HER2 positive the more likely it is that you will gain a substantial benefit from having access to Herceptin. You will, there will be a better response to the drug, and there will be better overall gain in life expectancy. But the question from an insurance company's point of view is, well how far down the line, that is going back on that continuum where somebody is a little bit HER2 positive, they may gain a little bit of extra life from having access to Herceptin. So insurance is asking, why should we pay for it, the gain is much too small to justify the high cost that might be associated with that particular with that particular drug. So there's a lot of uncertainty associated with the use of these drugs in spite of this being referred to as precision medicine. There's still a considerable amount of uncertainty at the level of the individual patient.

SM: Can you discuss the political challenges?

LF: Well the political challenges come in when we think about health care reform in the United States today. And so as I'm sure many of my listeners are aware of, we're having this debate about whether or not we should continue to push for more health reform and the slogan that's being used by many candidates for president United States among Democrats is “Medicare for All.” Now Medicare for all can mean a lot of different things and so we can't go into all those details right now. But if what we imagine is that Medicare for all would be something like the single payer system that they have in Canada, then the question is going to arise, what exactly is going to be included in the benefit package that will be covered by Medicare for all?

It's not as if cancer is the only deadly and costly medical problem that individuals in the United States face. There are lots and lots of deadly medical problems. Typically chronic degenerative diseases of various kinds, diabetes, heart disease, various kinds of lung disease and so on. All of which also have very very expensive drugs and other interventions that are associated. And we are faced with a problem of escalating health care costs in the United States, and strong efforts to control health care costs. So we spent $3.8 trillion on health care in the United States last year, and that was approximately 18 percent of our gross domestic product. That represents a very large portion of economic activity in the United States. And somebody has to pay those costs, either as taxpayers, or insurance premium payers, as employers or employees. But those costs have to be covered somehow, and they're continually increasing. And so if we had something like Medicare for all, then somebody would have to have responsibility for deciding which particular interventions, which particular drugs, were in fact cost worthy and affordable from this larger public point of view.

SM: Lastly can you discuss some ethical considerations related to this topic?

LF: Well the ethics considerations again have a lot to do with the particular costs that are associated with these drugs. Again I'll remind everybody that pharmaceutical costs in 2019, this year, are projected to be approximately $450 billion. So this represents something in the vicinity of about 14 or 15 percent of total healthcare spending in the United States. And that's going up more rapidly than the cost of health care in other parts of the health care system. Now pharmaceutical companies, because we are a free society, a capitalistic society, in fact are free to charge whatever they think the market will bear. And this is something of a problem in that in effect, their argument is well as long as insurance companies are willing to pay the cost of these drugs then we can charge whatever we want for these drugs. And after all, these are drugs that are aimed at individuals with a terminal illness, and so these are desperate individuals, and so they may be willing to spend a lot more than individuals who have medical problems that are more amenable to less expensive kinds of drugs.

Now in particular, and this sort of takes us back to some of the political stuff, in the Medicare program, so health care for the elderly, back in 2005 the pharmaceutical company put a lot of pressure on Congress and was successful in getting two limitations in the Medicare program. One of the limitations was that when Medicare has to decide whether or not to cover a particular drug, they would not be allowed to consider the cost of the drug for purposes of determining whether or not that drug would be included as covered by the Medicare program. And so what that means is that the only things that Medicare could consider would be is the drug effective, is it better than whatever the current therapy is for say a particular form of cancer, and is it safe. Is it safe enough. Are the risk benefit tradeoffs reasonable. Those are the only two things Medicare can consider. The other thing is that in Europe, for example, most of those countries will bargain with the pharmaceutical companies with all of the covered lives. Germany has a population of 80 million people. They can go to a pharmaceutical company and say, if you want us to cover your antidepressants you're going to have to give us a 50 or 60 percent discount. Otherwise your antidepressant is not going to be part of our drug formulary. Medicare, again, is now forbidden by law from bargaining with its 45 million covered lives to extract comparable kinds of discounts.

For workers, a problem is that most workers cannot cover the huge co-pays that are associated with these drugs. Which means, then, that for relatively well-off managers and executives within a company who can afford these very high co-pays, that the other 70 percent that has to be paid for these drugs is at least partially paid for by these workers who are financially less well-off. Though they cannot actually benefit from having access to these drugs because they can't afford the co-pays. That seems unfair, that just doesn't seem right. The other ethics issue that we're struck with is that there are some individuals who are what we call super responders. And we have a faculty member who in fact at one point was diagnosed with a gastric cancer a number of years ago. Was told that he had 6 months to a year to live because he had metastatic disease, but then they discovered his cancer was HER2 positive. And so he was put on this drug trastuzumab, and wonder of wonders, this drug is proved to be, for him, miraculous. He's alive 7 years later every three weeks getting a $17,000 dose of Herceptin. And so over the period of 7 years he has racked up costs of approximately $1 million to $1.3 million dollars so far. He's a super responder, he is very much the exception to the rule with regard to most of these drugs. But the ethics issue comes up. If we could find a biomarker that would identify individuals before the fact who are going to be kind of poor or marginal responders to a drug, would that mean then that we would have an economic reason and perhaps an ethically justifiable reason for then denying that drug to those individuals. Because the likelihood of their gaining significant benefit would be somewhat remote. Not zero, but just somewhat remote. And making a decision in that regard is a very serious kind of ethics issue.

SM: It is my understanding that there have been certain circumstances where individuals have been denied coverage of certain medical treatments and it caused a great deal of backlash. Do you have any thoughts on how you can increase acceptance denying certain treatments to certain individuals or how we can make this fair?

LF: Well, the argument that I've made in a lot of my published work is that these are choices that we have to make collectively, as a democratic society, as a rational democratic society. Ultimately, all of us pay taxes, all of us pay into health insurance plans, and we have to collectively decide what's really worth it from the point of view of our own money and what we're paying into this system. So we have to have some public conversations. We have to be able to have those conversations respectfully without a lot of anger and without a lot of name calling and so on. And so I'm trying to organize some of those, and I hope to organize some of these in East Lansing and Grand Rapids in the early spring of 2020. Roughly the month of March and April. What I imagine, what I'm looking for would be roughly 25 individuals in each community who would be interested in having this kind of conversation. Talking with their neighbors about these issues and so on, thinking this through more carefully. It would mean we would have the same group meet for a period of four weeks, once a week for about two hours in the evening each time, and if this is something that you'd be interested in doing, if you want to talk about some of these issues, some of the ethics and political issues that are associated with these targeted cancer therapies and precision medicine, then send me an e-mail. And we'll see if we can include you in one of these discussion groups. My email address fleck, f-l-e-c-k at msu.edu. We would certainly welcome your participation. Thank you for your time and attention.

LM: Thank you for joining us today on No Easy Answers in Bioethics. Please visit us online at bioethics.msu.edu for full episode transcripts and other resources related to this episode. A special thank you to H-Net: Humanities and Social Sciences Online for hosting this series. This episode of No Easy Answers in Bioethics was produced and edited by Liz McDaniel in the Center for Ethics. Music is by Antony Raijekov via Free Music Archive.