Evidence-Based Oncology

Immunotherapy in Cancer Care: Understanding the Impact of Shifting Treatment Paradigms in the Managed Care Setting | Page 1

Published Online: March 20, 2014
Part Two
The previous issue of Evidence-Based Oncology (EBO) featured the first part of a condensed edition of a peer exchange on the future of immunotherapy in cancer care, which was convened by The American Journal of Managed Care. This edition of EBO features the rest of that exchange. Immunotherapy, according to the American Cancer Society, is treatment that uses the immune system to ward-off diseases such as cancer by either boosting the body’s immune system in general or by training the immune system to attack some specific cancer cells, and may be used alone or in combination with other chemotherapy regimens.

Panelists discussed the positive and negative aspects of using immunotherapy, traditional chemotherapy, and combination regimens. They addressed the importance of promoting both patient and provider understanding of immunotherapy. Finally, panelists discussed the cost associated with immunotherapy in cancer care.

The discussion was moderated by Peter Salgo, MD, a professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at NewYork-Presbyterian Hospital, New York City. The panelists included:

Jeffrey Weber, MD, PhD, senior member of the H. Lee Moffitt Cancer Center and director, Donald A. Adam Comprehensive Melanoma Research Center, Tampa, Florida

• Michael A. Kolodziej, MD, national medical director, Oncology Solutions, Aetna

• Daniel J. George, MD, Duke Cancer Institute.

Peter Salgo, MD, continued the discussion by asking the panelists to comment on the excitement surrounding the use of novel cancer therapies such as immunotherapy. Dr Salgo asked whether the thought process for funding the associated costs of the new treatments would be similar to traditional treatments.

Michael A. Kolodziej, MD, warned that excitement is tempered by a need to wait for evidence. Immunotherapy, he said, is not treated differently from other therapies from an insurance standpoint.

Michael A. Kolodziej, MD: I’m not an immunotherapist, so I’m waiting to see the results. I mean, I still remember when the IL-2 paper was published and we were going to cure renal cell cancer with IL-2. So I’m waiting to see what the results are. Do we distinguish? No, I don’t think so… We’re interested in what it’s going to mean to our members. Are our members going to get better?

Daniel George, MD: I think skepticism is healthy. We still give IL-2 in limited circumstances, but we’re frustrated by the limitations of the therapy. What we’re excited about are the advances which seem to be moving us faster beyond those limitations….This is the opportunity to move those therapies that are doing some remarkable things, granted maybe not in everybody, but in a subset of patients with advanced metastatic disease, to earlier settings.

However, we have to meet a bar, and we have to pass the standards set by both skeptics and our regulatory agency. We owe that to all the future patients out there that those bars are met. However, what we are frustrated by is when we have met those bars and when people are still skeptical because this doesn’t fit the paradigm of traditional chemotherapy and shrink the cancer 20%, and therefore, I know it’s working in those circumstances.

Dr Salgo asked for comment about the fact that, compared to traditional chemotherapy, immunotherapy is subtle and quite well-tolerated.

Jeffrey Weber, MD, PhD: The effects depend on the situation. You might see tumor responses with PD-1 or PD-1 plus ipilimumab that are almost as impressive as you would see with  chemotherapy or targeted drugs. You can see responses that happen rapidly and steeply. So we’re in a different realm, and as we expand the repertoire of drugs available to us, you’re going to

find that we will be able to overcome the skepticism.

Dr Salgo nudged the panelists to discuss the safety profile of immunotherapies. Traditional chemotherapies shrink the tumor burden but are associated with a lot of side effects. On the other hand, immunotherapy has a good safety reputation.

Dr George: A cancer patient wants to live as long as possible, and he wants the quality of life, with not much concern for reduced tumor burden or slow progression. We have patients with a tumor burden that have a fantastic quality of life and they’re going along just fine. As long as that quality of life is going along and we’re not seeing any detriment in terms of either the disease progression or their cumulative toxicities, we’re achieving their goals.

So, to me, tumor regression is probably the least valuable of all the surrogates that we tend to use in our practice….

Dr Salgo continued the discussion by commenting that although it made sense that living with a tumor burden may not affect survival and wellbeing, he had never heard an oncologist endorse the concept.

Dr George: Well, let me qualify this that I’m a prostate cancer doctor. For the longest time, we’ve had bone scans that don’t meet RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

They don’t even represent the cancer, they represent a reaction around the cancer, the calcium deposition around the cancer. And we’ve had (PSA) prostate specific antigen as a biomarker. We really haven’t had measures of tumor burden, and it’s actually been the biggest hindrance to drug development in prostate cancer over the last 30 years, and we’ve just finally gotten over that in the last 10 years. So, I’m probably a little bit of a different oncologist than maybe what you’ve heard before.

Dr Weber: Although, to be honest, reduction of tumor burden is usually not regarded as an end in and of itself; it is a surrogate or a substitute for the greater variable, which is obviously survival and progression-free survival. … On the other hand, there are plenty of patients who present a significant decrease in morbidity and improvement in their symptoms and increased quality of life when they get some tumor reduction. So it can be a desirable endpoint, and the FDA (US Food and Drug Administration) does recognize, in single arm studies, that tumor reduction is an acceptable end point. They much prefer the ultimate end point, as they’ll always tell you when you meet them, of survival in a well-controlled, well-conducted randomized trial. So I agree with

Dr George in principle; response is not the ultimate end point but it can be a useful end point.

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