Immunotherapy Cost Problem May Require 'Revolutionary' Remedies

Jeffrey S. Weber, MD, PhD: Hello, I'm Dr Jeffrey Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University Langone Health, and co-director of its melanoma research program. Welcome to Medscape Oncology Insights. Joining me today is Dr Omid Hamid, chief of translational research in immunotherapy, and director of the Melanoma Center at the Angeles Clinic and Research Institute in Los Angeles. Welcome, Omid.

We talked about pharmacoeconomic issues with new immuno-oncology drugs. While there is an arithmetic increase in benefit, there seems to be a geometric increase in the cost of these drugs and in pricing. What do you think are some solutions to this really difficult problem?

Solutions Start With Trial Design

Omid Hamid, MD: One solution is to proactively answer these questions through clinical trials. Previously we discussed the example of exponential rising costs associated with giving all patients adjuvant therapy. We don't know if early therapy helps or if we can wait until there is a recurrence. KEYNOTE-054^[1] is a great example of a trial that will help answer these questions. It's looking at giving early anti-programmed cell death-1 (anti-PD-1) in the adjuvant setting for stage III melanoma versus waiting and then giving anti-PD-1 therapy on relapse. This trial has two arms that are equally weighted and has the endpoint of overall survival. Although patients not getting therapy upfront are fraught with anxiety, it spares toxicity. It will set the benchmark for how we will approve adjuvant therapies in the future.

Weber: I'm not so sure that you could have done that trial in the United States. As you know, that is an EORTC trial that was done primarily in the European Union. You could certainly do it in certain parts of the world, but I would have some difficulty proposing such a study with my patient population because (a) it has a placebo-controlled arm and (b) [I would be] telling them that they can be treated now or we can put treatment off until relapse. Although potentially problematic, it's a question that needs to be answered. It will be answered. I think it's a trial that had to be done.

'Relapse as a Biomarker'

We are essentially using relapse as a biomarker. Obviously it gets expensive if you treat four patients to benefit one, as in most adjuvant trials where the hazard ratio is 0.5, like COMBI-AD,^[2]KEYNOTE-054,^[1] or CheckMate 238.^[3] If you wait until everybody relapses, now you are treating two to benefit one. We need to do a better job of selecting the patients. We treat a lot of patients who are not going to benefit, and right now we don't have very good biomarkers.

Hamid: Agreed. In the metastatic setting, there is a rush to start therapy, and the possibility of getting the right biomarkers in time to let you choose therapy is difficult. In the adjuvant setting, you have tissue and the ability to wait and select the correct adjuvant therapy and avoid cost and toxicity. For the future, these adjuvant trials need to have high predictive biomarkers. One solution can be that regulatory authorities say that they will not accept it unless the benefits, even though they exist, are of a certain magnitude.

Increasing Value of a Treatment

Dr Weber: Talk to me about value pricing. In other words, there are many ways you could increase the value of a treatment. You could do a better job of selecting the patients, you could only pay for a certain outcome. What would be proposed solutions up the road?

Hamid: There are solutions out there that say to pay for outcome. [Reimbursement for a] patient making it to a year without relapse would be at a greater rate than if the patient went forward and got treated for a set amount of time. Then the reimbursement would be a fraction of what it would be fully.

There is also this idea that in one setting the reimbursement is different from in another. Could it be different in an adjuvant setting, where you know that there is going to be x-number of doses incrementally versus a metastatic setting, where most of the patients only get treated for a short amount of time? You re-image, they have recurred, and you move on. So the financial toxicity is lessened.

A third way would be to decrease the reimbursement for a drug on the basis of the number of indications and the market share that it holds. All of those things again may be revolutionary, but we need to have these discussions. This is an issue in a market where there is no competitive pricing—which is to say, similar drugs are reimbursed the same and they cannot outcompete based on price. That does not exist in other countries ex-United States. There are countries that avoid it and refuse to approve drugs that had survival advantage based on the financial toxicity that it would bring to its people. An example of that is anti-CTLA-4 in France. There are countries that negotiated better pricing than we have here.

Weber: Yes, we can't really do that. I'm always told that it's not allowed by federal law to negotiate a price for a drug. But your point is that that may change in the future.

Hamid: In the past, we had drugs that became generic earlier. Remember, these drugs now [take a] longer time to go to generic. In the past, when we had few options and few patients who would be able to get those options, that point was valid and could stay. At this time, there is a major change. We are, thankfully, helping more of our patients. We are, thankfully, making advances in the metastatic setting, and those are coming to the adjuvant setting. We have to do a better job in preparing the whole system for the financial possibilities.

Weber: A final interesting point is that the system—your practice, my medical center—is essentially addicted to us being able to prescribe these infusion drugs. They bring an enormous amount of revenue to the institutions, and they could not do without it. It goes both ways. Companies do well and then the institutions do well. There is not a vested interest to cut the costs and to change the system. Although, interestingly, I was at an ad board promoted, perhaps, five5 years ago by a large pharma company, where all of these suggested solutions for value pricing came up. Yet, I have not really seen much movement in that direction. It sounds like it's time to start moving again.

Hamid: I would agree. The movement has to come regardless of those ancillary issues. They are major, and we need to then move on to that as a separate issue. And we have to insist on better reimbursement for other things that we do at our cancer centers, like survivorship, supportive care, social work, and time and education.

Weber: Do you know where the movement is going to come from? It will come from the professional societies. It will probably come from the American Society for Clinical Oncology (ASCO). You raise an interesting point.

Omid, thank you very much for joining me today. This has been a fantastic discussion. And thank you, the audience, for joining us. This is Jeffrey Weber for Medscape.

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