'We Can't Have It Both Ways': Len Saltz on Hype vs Hope, Drug Costs, and ASCO 2017

What a difference a year makes. The last time oncologists from around the world gathered in Chicago for the American Society of Clinical Oncology (ASCO) meeting, the national conversation around healthcare, and cancer specifically, was markedly different. ASCO attendees were anticipating a special address at the meeting from then-Vice President Joe Biden, who was launching a federally funded cancer moonshot program through the National Institutes of Health (NIH). President Obama had previously announced the Precision Medicine Initiative, which was underway and placed cancer medicine as a centerpiece. The number of Americans without health insurance had plummeted following implementation of the Affordable Care Act, and the richest physician in America, Patrick Soon-Shiong, had also just launched his own "Cancer Moonshot 2020."

Cancer care, it seemed, was at the center of a historic national conversation.

Fast-forward 1 year. Both the Precision Medicine Initiative and the cancer moonshot are on shaky ground following President Donald Trump's proposed $5.8 billion NIH budget cut for 2018. Earlier this month, the US House of Representatives passed a bill to repeal and replace the Affordable Care Act. And Patrick Soon-Shiong is being investigated by the Utah state legislative auditor general following a questionable donation to the University of Utah.

In the context of these changes, Medscape spoke with Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York City, about ASCO 2017 and the major issues facing the oncology community. Dr Saltz is a leading expert on the cost of cancer drugs and will be presenting at ASCO 2017 in an educational session on financial toxicity.

Medscape: Last year at this time, a number of major cancer-specific initiatives were either launching or underway; cancer medicine felt like it was at the center of a national conversation. Was the mood of oncologists and the oncology community then different from this year, in which the national conversation around healthcare feels like it has a markedly different tone?

Dr Saltz: To say that there is a prevailing mood one way or another is maybe too simple. Of course, any of us who work in cancer research or cancer care have to be maintaining a degree of optimism and a sense of purpose that we're going to take the situation that we have and figure out how to make it better. That's what we do. That's what I get excited about and get out of bed in the morning for. That doesn't mean that I think there is any one simple solution. So when somebody puts together the idea of a moonshot, and it means a way of progressively providing funding—hopefully high-risk, high-yield projects—of course I'm in favor. But I'm not naive enough to think, "Well, problem solved. I can go on to something else." I'm cautiously optimistic that it's going to bear some useful fruit. The Precision Medicine Initiative is a step forward, but in too many circumstances we're finding that people are expecting more out of precision medicine than is reasonable and fair to expect. It's not simply the case that we can look at every cancer, figure out a target gene, give a nontoxic therapy that hits that one problem, and solve the problem for the patient. We know that.

We've learned it the hard way. Ten years ago, we thought that was going to be more likely. It's simply more complicated than that. So, will precision medicine improve on the standard of care? Absolutely. Am I in favor of it? Completely. Is it the panacea that will solve the problem? No.

Of course, when there's a major commitment financially and politically, there's going to be some optimism and some hype. There will be some wishful thinking that's going to oversell it. That doesn't mean it was a bad idea; that doesn't mean we should give up hope; that doesn't mean we should abandon it.

Medscape: Do you feel that federal initiatives like the Cancer Moonshot or the Precision Medicine Initiative have been overly optimistic?

Dr Saltz: We as oncologists are always working with a need to strike a delicate balance between optimism, cautious optimism, and realism. Because when we're dealing with the fight against cancer, we're dealing with a very, very difficult fight. Within that context, we're trying to be doctors to arguably some of the sickest people on the planet. We're trying to offer emotional and physical support. We're trying to both do the best we can for people and help people understand the limits of what that is. That's a very, very delicate balance.

Most doctors do a very good job of striking that balance, but sometimes, especially within the context of meetings like ASCO, where we're trying to raise the bar and move things forward, as well as under the economic pressures of all of the various for-profit entities that are involved, the hype, if you will, can get a little bit out of hand.

We have hope, but we also have hype, and there is a gap between reality and perception.

Medscape: How does this play out in actual practice?

Dr Saltz: We have begun to use terminology that allows people to misinterpret what we're saying, whether they're euphemisms or technical terms that have come to be misunderstood. One of the most important is the term "significant." We frequently hear the phrase, "This drug provided a significant survival benefit." When I say there's a significant survival benefit, we know that most people will hear, "There's a substantial survival benefit." Unfortunately, the two are not the same.

We have an awful lot of treatments that are offering less than 2 months' survival benefit, and I would argue that less than 2 months' survival benefit is not clinically significant. There's a lot of pushback on that. Not everybody agrees. If our feeling is that any survival benefit is clinically significant, then I think we're in trouble because we then circle back to what this costs and what it ultimately prevents us from being able to provide to our patients because of these costs.

We also often use the term "progression-free survival" as an endpoint for studies. Progression-free survival really should be called, in my opinion, the progression-free interval, because it's the amount of time from when you start a treatment until it's no longer helping the patient.

We use it a lot as an endpoint where we want to believe that it's a surrogate for overall survival. And we very comfortably allow the audience listening to us—whether it's our patients or a larger audience of professionals—to misconstrue that we're talking about survival. Of course, when patients hear about survival, they think we're talking about an increased cure rate. Unfortunately, that's a different term that we don't get to use enough in this business. When we're talking about advanced metastatic solid tumors, that's still very rare, unfortunately. The degree to which one chooses to push that inconvenient truth aside has a lot to do with how much positive versus negative spin you might have when approaching a meeting like ASCO.

I don't think anybody would disagree that one of the most important developments in cancer care over the past few decades has been the advent of immuno-oncology. For decades, patients have been saying, "Can you just rev up my immune system to fight this cancer?" We didn't really have any understanding of how to do that. Now, at least we can look at immune checkpoint inhibitors—CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors. We have drugs that can really do that for some people. But the degree to which the public has decided—or been convinced—that immuno-oncology cures cancer and solves the problem, without side effects, and can help everyone and can help keep everyone alive is just not consistent with the reality.

It's great when we can help some people. Unfortunately, out of wishful thinking, everyone assumes that once we've got something that's helping one group, it ought to help everyone. I only wish that were true.

Medscape: What are the costs of buying into this hype, or wishful thinking?

Dr Saltz: Nobody wants to belittle the advances that we've made. But we do have to keep them in perspective. When I make a statement that I'm not satisfied with a 1.4-month survival benefit, it's because I don't think it is clinically meaningful. An argument that comes back is, "Well, it's the best we've got."

I think that's a self-defeating argument. First, we've now seen enough situations where some of the new drugs in certain settings are offering much more substantial survival benefits. That's real. That needs to force us to go back and re-evaluate whether we should be accepting something that has such a small survival benefit.

The other problem is that if we accept very small survival benefits, that's what we're mostly going to get. From a business-model perspective, it's easier for a biotech or pharmaceutical company to aim for a small advance than a large one. If we're going to reward them equally well, it's a much better business strategy to go for a small one, to go for a subtle variation on an already established theme, a little bit of advancement, rather than encouraging real innovation and asking these companies to take a risk for a bigger reward—going for the big hit rather than the bunt single.

We can't have it both ways. We can't just keep rewarding everything that gets a P value greater than .05, even if the difference is clinically trivial, and expect that that's going to move us towards drugs that have really big, really meaningful advances for patients.

It's a balance because when you say, "It's not worth it," obviously someone is going to be angry and offended and say, "Well, not worth it to whom? It's worth it to the person who gets it." The answer is, yeah, perhaps, but as a society we're all in this together, and effectively we're all paying for this together.

Medscape: The NIH, which funds cancer research through the National Cancer Institute, appears to have gained $2 billion in funding for 2017 in a bill that President Trump signed earlier this month. However, President Trump has proposed cutting $5.8 billion from NIH's budget for 2018. What kind of effect would a cut like this have on clinical research?

Dr Saltz: Everybody loses if we don't have peer-reviewed, government supported research. Too much of the responsibility for drug development has been handed off to or usurped by industry, and that creates short-term profit motive, which is not necessarily the best engine for long-term therapeutic improvement. The need for government-supported, peer-reviewed research has never been greater; anything that increases that is going to be for the public good, and anything that decreases that is going to be against the public good. Obviously, if everybody agreed, then we'd have no problem. So, obviously there are people who disagree with me. That's my feeling.

Medscape: What effect do funding cuts like these have on investigators?

Dr Saltz: One of the effects that it can have is that for many in the academic world, in order to stay in the academic world, you have to be able to get government grants. If those grants aren't available, then some of those people are going to have to leave and go into other forms of work. You can lose really creative, really good people. It also discourages young, bright people from going into the field. You've got to have the ability to succeed for people to want to get into the competition.

It also makes it very hard to select research projects to fund. I've been on grant review committees where we're looking at 115 grants and we have the money to fund three. It's easy enough to figure out the top 15 or 20. But from there, you almost feel like we should throw it to the ceiling and see what sticks. If you have more generous funding, then you have room to support more creative ideas. If any one idea was obviously going to be wildly successful, we would have no problem. But, of course, the very nature of research is that you don't know what's going to happen until you do it.

Medscape: What's the most significant issue facing oncologists today?

Dr Saltz: I don't know that I have an answer for you. I don't know that I can distill it down to one thing. And again, you have to remember that oncologists are a heterogeneous group of people. So I don't think that there's any one issue.

I do think that everybody is concerned that there is an enormous amount of time lost in the documentation and approval processes—the combination of the electronic medical record, which has paralyzed many people in terms of the amount of time it takes up, and the hoops one has to go through for approvals for each drug, each scan, and so forth. It's very time-consuming and a problem that many people feel.

More and more, people are also becoming aware of the costs involved in some of these treatments. It's hard to see how this can continue. I think and I hope that more and more people who take care of patients are becoming aware that the patients are not insulated from the costs. I think we've had this fantasy that if a patient has insurance, all the cost issues are somebody else's problem. The word's gotten out that financial toxicity is a real toxicity, that a cancer diagnosis is a leading cause of personal bankruptcy in the United States, and that the financial issues are very real.

Another issue to think about: We use the term "quality of life," but we don't really stop to think about it enough. When I think about what we're trying to do for patients with cancer, there's been a lot of focus on lifespan but perhaps not enough appreciation of the importance of the health span—how long we are able to keep a person functioning and feeling well at a high level.

That's where I think our efforts need to be focused. I'm worried that as we've gotten comfortable with third-, fourth-, and fifth-line therapy for each metastatic cancer, we're losing sight of what that existence is like for our patients and how difficult that is for them.

Medscape: The issue of cancer drug costs has been on the cover of news magazines for several years now; everyone is familiar with the issue. What, if anything, is actually changing in the cancer drug–cost conversation? Are there any solutions that are having any effect, or are costs continuing to escalate unmitigated?

Dr Saltz: It's hard to answer your question specifically. What I could say is that no one would pretend that the problem has been adequately addressed or solved. The cost of drugs is continuing to go up at a very rapid rate. It's not only the cost of new, expensive cancer drugs; the costs of generic drugs are going up astronomically as well. I think people are going to become more and more aware of this as it starts to hit home through situations like Valeant Pharmaceuticals, Turing Pharmaceuticals, and the EpiPen story with Mylan. It's getting harder to push forward our arguments that these are isolated apparitions. These are indicative of what the industry is doing quite frequently. It's not hard for me to come up with a list of dozens of drugs that have had very, very, very substantial price raises. We're also seeing this reflected in situations where drugs that are relatively inexpensive are too often going into national shortage, which is forcing the use of more expensive drugs. We're in a situation where it's totally unsustainable. We haven't made the changes that are necessary to create a sustainable healthcare environment. I worry—I don't have a clear vision of what happens when we reach a point where we just don't have the ability to get these drugs to the people who need them. I worry very much that we're creating even greater healthcare disparities between those who are wealthy and those who are not, in terms of what treatments are available.

Medscape: As experts on issues of drug costs and the value of clinical research, do oncologists have a professional obligation to publicly address these issues, or is that a personal choice?

Dr Saltz: It is very hard for any one person to tell somebody else what their obligation is. So I really wouldn't want to do that. I feel obligated, I feel that it's the right thing to do. But I'm in a different situation from many other people who might be in private practices or in other aspects of their career. I can't pass judgment on whose responsibility it is or is not. I do think we need to understand that drug companies, being publicly held companies, have fiduciary responsibilities to their shareholders to raise their shareholder value. They're doing their job. Unless we can make people aware of the damage that's occurring as a result of that, we can't say that it's the drug companies' problem to solve.

The problem is that it's become a very unlevel playing field at this point. The pharmaceutical industry has enormous political lobbies, enormous financial resources engaged in those political lobbies, and really enormous resources in direct-to-consumer advertising, which I think is one of the biggest problems that we have. The American Medical Association has come out against direct-to-consumer advertising in the pharmaceutical world. I strongly agree. The ads work to create unrealistic expectations and to push demand beyond where it should be—to push for use of drugs in places where it's not really the right thing to do. I think that everybody involved in the cancer world has a reason to want to see sustainable cancer progress, cancer care, and availability of that care to be provided to everyone who needs it. If everybody thinks that somebody else will solve the problem, everybody is going to be set up for disappointment.

So, I hope that enough individuals from enough places will decide to put their energies toward addressing this problem, because nobody has a simple, easy solution and nobody has a solution that isn't going to be resisted by somebody; if I save money somewhere, somebody else is losing that money.

Medscape: Where would you personally like to see ASCO direct more of its energy in terms of advocacy?

Dr Saltz: I would like to see all professional organizations try to address the problem of access to quality care for everybody and control of the cost of that care. I've focused most of my energies on drug prices because it's what I have some expertise on and what I've been dealing with. But there are many different aspects of the problem. I think it's great to be focusing on trying to make improvements, but we have to work on getting those improvements to everyone who needs them.

Over the past year, I've been asked to lecture to a number of groups involved in translational science in cancer care on the cost of care. I've been using the title "Drug Cost and Cancer Care: Why It Matters in Research." I put up a very simple slide about what we need for a drug to work. It's fascinating to see all of the iPhones come up and people taking pictures of it. The slide is just, "What do we need?" We need for the drug to work, meaning efficacy; we need for people to take it, which means tolerability and acceptability. If it makes people feel horrible, they're not going to take it. If they've got to take 27 pills before breakfast, they're not going to take it. It's got to be something they can take. And the last point is availability. Patients have to be able to get it, and that means they have to be able to afford it. If any one of those three doesn't happen, the drug doesn't work.

It's very simplistic, but it's an important way of thinking about it. If some just say, "Well, my job is to do the chemistry and somebody else will solve the cost problem," then I think it's worth being aware that the problem just doesn't get solved, especially when we start looking at combination therapies and saying, "Well, we know this drug isn't going to work, but what if we add it to these three other drugs?" Take a look at each drug coming out—we're averaging between $100,000 and $150,000 a year for these—and then to think we're going to need three or four of those? If you do the math per patient, people say, "Wait a minute—how can that work?"

It's a process to get people thinking this way because we've been trained for so many decades not to think this way. We've been trained for various reasons—some good, some not—that everything we do should be above consideration of cost, that somehow this is too important to worry about money. We've lost sight of the fact that, yeah, there are a lot of people whose businesses are involved here who are very, very focused on just how much money we're charging.

We can't have it both ways.

The interview has been edited for length and clarity.

Medscape Oncology © 2017  WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: 'We Can't Have It Both Ways': Len Saltz on Hype vs Hope, Drug Costs, and ASCO 2017 - Medscape - May 31, 2017.