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
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.

Dr Salgo continued the discussion by asking Dr Kolodziej to provide examples of cost effectiveness or quality-of-life data that would aid in these decisions on coverage and reimbursement. Additionally, he asked if money was the major driving force in the decision-making process and whether the benefit of therapies was underestimated.

Dr Kolodziej: As we discussed before, that has typically not been the process,  partly because it’s politically unpalatable.  In addition to poor quality of data, it is a difficult pill to swallow.

If a medicine invented tomorrow could cure cancer, people would get it. We would, as a society, decide it was worth it irrespective of what the price is. The elephant in the room is why do things cost so much money. We’ve heard the excuse that drug development is expensive and maybe that’s right. It’s not my area of expertise. Are we going to get at the ultimate cost of developing a drug? What a fair price is? Is the government going to step in?

Dr Weber: Part of it’s because so many drugs fail.

Dr Kolodziej: We will see. I don’t know where the truth lies, but I don’t think it’s an accident that everything costs $10,000 a month now. You said it yourself. It’s what the market will bear.

Dr George: When you talk to drug companies and ask, “How do you set the price? Why do you set the price so high?” They’ll come back and say, “We have to.” Like Dr Kolodziej says, it’s not

his money. He’s really just being a steward. They’re stewards of their shareholders, and their shareholders will come back and sue them if they don’t price that drug at what it maximally could be priced at. That’s the capitalist society that we have.

Dr Weber: It’s a very simple solution in the capitalist system: if nobody wants to buy your product, it doesn’t matter how much you charge—you’re not going to make any money. But if you drop the price and people start to buy it, then you might start to make some money.

Dr Kolodziej: But we’re going to see a very interesting thought experiment play out over the next 18 months with TKIs (tyrosine kinase inhibitors) and CML (chronic myelogenous leukemia).

Recently there was an article in Blood where the CML researchers went out there and said, these drugs are really, really expensive. We’re not sure why they cost so much more money. The new ones cost more and have small incremental benefit. So what’s the thought experiment? Imatinib goes generic in a year, which means that we’re going to have drugs like dasatinib or nilotinib that cost from $8000 to $10,000 a month and we’re going to have imatinib. And I don’t know what it’s going to cost. Let’s just argue $1000 a month or $500 a month. So should we step? Should we require people get imatinib first? Is there a reason not to do that? Now we have this scurrying going on about trying to define a value proposition for the newer TKIs. Yes, they have a better depth of response and a better molecular profile. The question though is if you start with imatinib, is there any risk to the patient of doing a step?

Dr Salgo furthered the case for immunotherapy by sharing beneficial data on Provenge. This therapy for prostate cancer resulted in fewer hospitalizations (1.2% versus greater than 26%), fewer discontinuations, and fewer deaths than AEs (adverse events) with docetaxel in prostate cancer. These data suggest that Provenge could save money compared to traditional therapy,

and it is only administered once.

Dr Kolodziej: People don’t get either/or. Talk about disingenuous. People know that there’s a lot more toxicity with chemotherapy. People who fail Provenge get chemotherapy later. It’s not the right question.

Dr Salgo: But take it the other way around. People who do well on Provenge don’t, and then it may be much more than cost-effective. Dr Weber?

Dr Weber: The benefit to Provenge is the same way they get docetaxel. The clinical trial that was done, these were clinical trial patients in the United States, and only 50% of them got docetaxel chemotherapy when that was really the only other approved therapy at the time for advanced prostate cancer. So I would just push back on Dr Kolodziej a little bit. I’m not sure that everybody is going to get every therapy with prostate cancer or even kidney cancer. If you look at our registry on kidney cancer, 20% of patients have third-line therapy. So  there’s a drop-off with each of these, and some of that is disease progression and death, and in some cases patients don’t want any more therapy. Considering the heterogeneity in this field, moving some of these therapies, particularly immunotherapies that have demonstrated the greatest value in the long-term survivors, to me makes the most sense. If you’re going to use those treatments, use them in a setting where they have the potential for that patient to live long enough to really get a more absolute benefit, whether it’s due to sequential other therapies or not.

Dr Salgo then asked Dr Weber’s opinion on the impact of the ACA (Affordable Care Act) on the coverage for cancer in terms of immunotherapies.

Dr Weber: Obamacare consists primarily of expanding the equivalent of Medicaid to a larger chunk of the uninsured population, which is a good thing. This country has a huge proportion of uninsured folks; I’m sure we have the highest share in the industrialized world.

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