Evidence-Based Oncology

Immunotherapy in Cancer Care: Understanding the Impact of Shifting Treatment Paradigms in the Managed Care Setting | Page 2

Published Online: March 20, 2014
Part Two
Now, is that the right thing to do? I don’t know. In some cases it’s futile. But we actually don’t know the answer to that question.

Dr Weber: It’s a testable question. All the more reason why Aetna should be supporting that kind of research.

Dr Kolodzieij: It is a testable question. The data that are required to do that is, it may sound simple, but it’s not so simple. So this is the heart of comparative effectiveness. And we will come to a point where those questions are going to get answered.

Dr Kolodziej said comorbidities make such answers complex, and costs may be spread in many places. But he agreed with Dr George that the real questions are: how much does it cost to take care of a patient with cancer, and what is the timeline? Patients who respond live longer and live better. Dr George said these questions affect how patients are selected for clinical trials.

Dr Salgo then specifically asked Dr Weber to explain some of the factors that would determine a product’s cost versus benefit.

Dr Weber: Well, the cost is obviously set by the pharmaceutical company; as Dr Kolodziei said, the process is ambiguous. Although, my gut, by the way, is it’s whatever the market will bear, and we do live in a capitalist economy. The FDA explores this extensively because they’re always thinking risk-benefit. That’s the charge of the FDA and the Code of Federal Regulations.…However, we think about this as oncologists. Can I take an 85-year-old and give him ipilimumab if he’s got Crohn’s disease? Well, that’s probably not going to happen. So I have to always make the assessment, as all of us do as physicians, of will a patient be able to tolerate a drug, does the drug have more than marginal benefit, and what’s the likelihood it’s going to prolong survival with a decent quality of life?

Dr Salgo then asked the panelists to define meaningful improvement. What is reasonable improvement if the length and quality of life is weighed against the cost of treatment?

Dr Weber: Well, I think most people in the business would say, as a rule of thumb, if you have a prolongation in survival with a hazard ratio of 0.75, meaning you have a one-third increment in survival over the control group, that’s probably meaningful. However, if that increment is weeks or a month, forget it. If that increment is months added to a baseline of a year, then yes.

If someone said we’d like you to do this, you’d live a year with the control, 15 months with the drug, which is a 25% or a 30% increase, I’d say, that’s reasonable.

It’s marginal benefit, and Americans are willing to pay a certain amount of money in general per year of qualityadjusted life gained. And that turns out to be $50 to 150,000. If I told you, as the consumer, that, well, we’re going to give you this therapy to prolong your life by 6 months but it’s going to cost $500,000 and there were a couple of hundred thousand of you in a survey, you’d probably give it thumbs down.

Dr Salgo asked whether the government or the provider is obligated to honor the patient’s decision to follow up on an expensive treatment. Where do you draw the line?

Dr Weber: It’s not clear to me whether I am obligated to honor that as a physician.

Dr Kolodziej: So Aetna doesn’t draw the line and neither does the government, because there has not been political appetite in this country for doing that. In the UK there’s an organization called NICE (National Institute for Health and Care Excellence) that sets a threshold for what constitutes reasonable. We do not do that in this country, and I don’t know if we will. But the NICE experience has led to alternative approaches to paying for expensive therapy. (In some cases, payment is not made until a therapy is proved effective.) Could I envision this in the United States? Maybe, but there’s other ways that people have talked about it, such as value-based insurance or referenced pricing. Let’s say the federal government says, all right, we pay $12,000 for this. Anything that you want that costs more than $12,000, it’s on your nickel. With value-based insurance, if it’s curative therapy, you pay nothing. If it’s therapy that has little benefit, you pay most of it. People have a hard time with those constructs. There’s a lot of emotion tied up into it.

Dr Kolodziej said Aetna is not doing this, but there is a lot of discussion about the concept. Dr Salgo asked Dr Kolodziej about why the provider might reject the upfront onetime cost of immunotherapy, which has proved successful, when traditional therapies keep incurring cost due to extended regimens.

Dr Salgo also asked whether risk is being shifted from the payer to the provider and consumer.

Dr Kolodziej: The answer is that that is speculative and actually that work hasn’t really been done….What we know is that some patients have durable responses. About 10% of patients have durable responses. So you got 90% who got treated with a very expensive drug and are going out to more expensive therapy. It’s not simply, oh, well, it’s clearly worth it because 10% of people are (responding). I’m not shifting risk anywhere. I’m just telling you the options that are out there. Remember, you’re the payer. I’m not the payer. We’re not spending Aetna’s dollars. When the government pays, they are spending taxpayers’ dollars. It’s very important to remember that because, ultimately, it’s a societal decision…

Dr Salgo asked who drives decisions on treatment: the patient, the provider, or the payer? How are options presented?

Dr Weber: I don’t believe that everyone will be in a position to make that decision; this is a societal decision. Our country and most other countries will need to make decisions on where you put the resources, and I think those decisions are going to be made for us. I don’t think, as an oncologist, in 10 years, I’ll get to choose to treat someone with a drug that cost $300,000 that will prolong life, on average, by 2 to 3 months. I’ll be in a position where I can spend a fair bit of money, but I have to have a high degree of assurance that I’m going to benefit the patient at a modest cost, in terms of toxicity.

Dr George: This is going to have to fall back on the provider, because the variability here is the tumor. There’s incredible heterogeneity. There’s no way our patients are going to have the wherewithal to make a value decision about their cancer, and their life, and their cost without the information that we have. And so I think we’re going to have to be, as providers, part of that decision process. But let me just say that I think the problem that I see happening is that there are already situations where this is coming to fruition, with capitations or other things. And, as a society, we really haven’t addressed this...

Dr Kolodziej: There is no reason that an oncologist should be uncomfortable talking about the cost of care with their patient. Let’s face it, in the current system, as imperfect as it is, medical bankruptcies are skyrocketing. So, we’re not doing our job right if we’re not telling patients what they should expect in terms of cost...

Dr Salgo then initiated discussion on the use of combination regimens and how the combinations, including immunotherapy, are impacting resource allocations. Panelists were asked whether an evidence-based method exists for determining this cost-benefit ratio for the various possible combinations.

Dr George: I would think of combinations with immunotherapy differently than the way we thought about combinations with traditional therapies, or just chemotherapies or targeted treatments.

Getting back to what Dr Weber alluded to, whether it’s a single dose or there’s a series of dosing that happens, a treatment effect subsequently emerges. So you could think of combinations with ipilimumab as happening after the ipilimumab is done, whether it’s radiation, or chemotherapy, or other strategies.

The same is true with Provenge. I’m not sure we necessarily have to think of combinations in the same context as what we thought of before. Now, there are targeted therapies that don’t work that way. They work as long as the drug is on and when the drug is off, they stop working; so the combinations have to be synchronous. Immunotherapy is not that paradigm. So we should think about this, not in terms of upfront cost, but as the cost over the life span of that patient, and all the subsequent therapies, as being a combination.

Dr Weber: (We’re hearing about) the first simultaneous combination of PD-1 and (ipilimumab);…It has a pretty high response rate between 40% and 50%, and a 50% dose-limiting toxicity; but those patients will live long. The combination is already being developed in phase III studies, with durable responses and survival being the endpoints, and those endpoints will probably show that there is a benefit to doing some combination of immunologic therapies.

The question is: if ipilimumab is $140,000 a year for the wholesale price, can we imagine the cost of PD-1? What if it’s an equal cost? PD-1 is administered every other week for multiple weeks.

What if it’s $300,000 a year? Can we afford that? That’s a tough one.

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