John L. Marshall, MD; David J. Kerr, MD; Tony Mok, MD


June 12, 2012

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John L. Marshall, MD: Hello. I am John Marshall, Professor of Medicine at Georgetown University and Director of Clinical Research for the Lombardi Comprehensive Cancer Center in Washington, DC. Welcome to this Medscape Oncology Insights Roundtable, coming to you from the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO®).

The focus of today's discussion is global oncology. Is a collaborative international scope of oncology in both research and patient care of benefit to us all? What are the challenges going forward in understanding global oncology?

Joining me are 2 outstanding colleagues with a true international perspective on this subject. First, Dr. David Kerr, Professor of Cancer Medicine at the University of Oxford, and past president of the European Society of Medical Oncology (ESMO) -- and quite a good friend. David, welcome.

David J. Kerr, MD: Indeed, John. Thank you.

Dr. Marshall: Also, Dr. Tony Mok, who is Clinical Professor at The Chinese University of Hong Kong and the Prince of Wales Hospital in Hong Kong, and Vice President of the Chinese Society of Clinical Oncology (CSCO). Tony, thanks for coming.

Tony Mok, MD: Thank you so much.

Getting a Handle on Global Oncology

Dr. Marshall: It is really a pleasure to have you both here, but I want to pick on David first with a really hard question: How would we define global oncology? What does it mean to you?

Dr. Kerr: For 2 years, I was president of ESMO and that gave me a fantastic opportunity to travel, so I got to meet Tony. We have become friends and we have built relationships between our societies. During these 2 years, I had a chance to visit every element of the globe -- oncology tours -- it was almost like that. For me, globalization is about convergence.

We all inhabit the same global village. We are all part of the same community, and it is a convergence of science, translational work, basic work, and clinical work. You can see that scientists working in China or Georgetown or Oxford have a set of common aims and values to apply our knowledge and wisdom as best we can for our community of patients. If we look at cancer patients, whether in Beijing, New York, Hamburg, or wherever, they have the same set of needs and requirements of us, so there is something about convergence of quality, of us driving our science and medicine forward, of meeting the needs of our patients.

Perhaps what truly demonstrated it to me were some of the inequities. Clearly, we move in high-quality, very strongly knowledge-oriented societies, in which our healthcare systems can support most of what we do -- new drugs and new ideas. We know that even within our own countries there are inequities between rich and poor, but these are amplified if we travel to sub-Saharan Africa, to some areas of southeast Asia, to the Vietnams and so on; therefore, there is an element of global oncology, which is about recognizing that imbalance. We need to look to leaders, like ourselves, to see what we can do to redress that imbalance and work together to truly drive the global oncology agenda forward.

Is Cancer Care a Luxury Item?

Dr. Marshall: When I think of oncology care around the globe, it feels to me like a luxury item. There are only certain parts of the world that really have cancer care to the level that we westerners have. Tony, give us a little insight about the evolution of cancer care in China -- and in Asia in general -- and the impact that it is having on both patients and governments.

Dr. Mok: It is a very difficult question because, in a sense, even within China, it is very heterogenous. It can range from people living in the mountain and rural areas, who hardly see a doctor, much less an oncologist, to the high-power very high-quality healthcare in Shanghai and Beijing. So, that is a big spectrum. An interesting phenomenon is that even people from the rural area, once they get ill -- a serious illness like cancer -- they may just move to Beijing or Shanghai and seek care if they can afford it. But obviously, a majority of the population cannot afford to do that and can get only minimal medical care or traditional Chinese medicine. So, it is very diverse and heterogenous, even within China.

The question is, just like what David alluded to, how can we minimize the imbalance? Within China, CSCO has an educational program going out to the rural areas, trying to educate the local doctors about basic care; this is one of CSCO's efforts over the years. At the same time, CSCO also tries to assist the more powerful centers to improve further to attain the so-called "western standard." So, there are actions being taken but the disparity is still wide.

Dr. Marshall: We are struggling with innovations that come at a high cost. Now, even in the United States, we are deciding that we can't afford an increasing number of costly innovations, so we are being forced to define value in what we do, both in the things that are already in place and those innovations that are being introduced.

How do we make room, under the cap, to bring in innovation? David, I know you think a lot about this. Give us a little perspective from your side about how we are defining value, how you would define value in cancer care, and how it is being played out in different parts of the world.

Value on a Sliding Scale

Dr. Kerr: Thank you, John. For me, value is about the clinical outcomes and how we measure those, so it's about outputs, not inputs. But it's the cost associated with those outputs. One of the things that we have done in the United Kingdom is invented this organization called the National Institute for [Health and] Clinical Excellence (NICE), or "Not So NICE," as it is known internationally. This represents a transparent means of judging the relative value of a new modality of treatment, whether it's imaging, biomarker-driven treatment, or whatever it might be.

The beauty of it is that it is transparent. There is a very strong methodology underpinning it. Citizens can add their voice to whether something is a good idea or not, and it allows us, within a socialized healthcare system, to say that this is what we think we can afford for this set of benefits. We set these benefits against not only cancer treatment, but also the benefits of hip replacement in elderly women, replacement of a lens for somebody with glaucoma, and so on. NICE looks at the totality of healthcare. None of us is an island unto ourselves and it serves us to look at things in that way.

The beauty of NICE is that it could be scalable. If you are a very wealthy country, you can set the scale up here. If you are a relatively poor country, you set it down here. It allows a set of rules and a set of guidelines that we can argue about, but at least they are obvious. It is not rationing through the backdoor. It is not saying one thing to the wealthy and another thing to the poor. It's clumsy, I know, but the intention is a one-size-fits-all methodology. We could apply it to Beijing or to rural China, as well as to Georgetown.

But Would You Pay for It?

Dr. Mok: I agree, kind of, but only under the umbrella of nationalized medicine. In a sense, when government is paying for everything, then of course you have to go by the rules because it has to be fair for everybody. In Asia, particularly in China, although we have nationalized medicine, in fact there is a lot that the patient has to pay for out of pocket. So under those circumstances, a lot of this has to be the value of the treatment vs what you have to pay, and you have to come in with a lot of honest evidence.

There is a randomized study showing that there is improvement in median survival of 2 months. Is that valuable or not? How do we [as oncologists] make that judgment? Or should it be a personal judgment?

There are 2 extremes that we are directing. One extreme is that we have to drive science that makes a big difference, such as a specific therapy for a patient with an oncogenic driver. That will make a huge difference to the patient. We have to push for that and make it more available to the general population vs something that results in some improvement, but not a huge improvement. Then we have to make it optional. We try to be neutral and nonbiased, in terms of outside influences in how we persuade the patient to take or not take the medicine, so the whole thing is actually quite complex.

Controlling Cancer at $8 per Head

Dr. Marshall: I am hearing a 2-tiered approach. On one hand, you have a government validating or endorsing a certain therapy vs the freedom to choose that therapy. There needs to be at least some base for the general public. The base could be different, depending on each individual country, with an opt-in; even in Britain, you have "opt-in" options for those who can afford to pay. So we do have somewhat of a 2-tiered system.

Dr. Mok: We have a Chinese translation of the National Comprehensive Cancer Network (NCCN) that has been adopted by CSCO, but we have no regulation that requires people to follow it. Once you are in a nonnationalized system, although you have guidelines, no one really pushes you to follow the guidelines. That is the difficult part of it.

Dr. Kerr: Tony picked up on 2 interesting elements. One is how we, as practicing oncologists, present data to our patients. We are not population doctors; we are real physicians with real patients sitting across the desk from us, and part of the issue is how we talk about benefits. An interesting debate -- for another day -- is whether we should give our patients the absolute benefits of treatment or the relative benefits. When we say "a 25% improvement in survival," that sounds fantastic, but the reality is 6 weeks.

I also have a bee in my bonnet about guidelines, like the NCCN guidelines. They're well worked through, rapid turnover, excellent panels running them, but they are set too high. When I was visiting in Malaysia in Kuala Lumpur and Vietnam, our colleagues there were saying, "Please work with us to develop a set of guidelines that will be affordable for the mass of patients that we look after." I listened to John's idea of 2 tiers. That seems okay to me. But I would rather say that there is 1 set of guidelines. This is for all, and if we can't measure them, then it's suboptimal medicine. Cheaper medicine isn't bad medicine. It's not. You do the best you can with the tools available and that the patients can afford.

Should we be looking for guidelines for the rural poor of China, Mexico, the southern United States, the United Kingdom, or are we abandoning them because we are elite? Does that mean that we are reducing our standards?

Dr. Mok: Is there a guideline from ESMO that's called "minimal"?

Dr. Kerr: Yes.

Dr. Mok: Exactly. That is the framework that we can work with. It's actually an excellent idea.

Dr. Marshall: At the meeting here, there was a presentation during which one of the speakers asked, if we were the government panel who had to decide how to spend our government’s money, would cancer even be on the list? Would vaccinations and other infectious disease priorities trump cancer? In an emerging country with an emerging population, cancer care may be primarily prevention, and therapies a sideline. Do you think that is true?

Dr. Kerr: What a fascinating discussion. If we were writing a cancer control plan for Malawi or Kenya, the Kenyan Health Minister has $8 per head of the population to spend on all of healthcare. Where does cancer fit in with that?

If we sat down, we would say that there is something around awareness-raising and prevention, vaccination, and treating the treatable and curable. Go after the kids because we know that even with minimal treatment standards, we can cure a lot of the kids. The cure rate for pediatric cancer in our wealthy countries is 85%-90%. In Africa, it’s less than 5%. By using cheap generic drugs, we could increase that percentage, so we need awareness-raising and prevention. Let's go for the kids and palliative care. Access to morphine is still difficult in many countries.

Clinical Trials: East Meets West

Dr. Marshall: We all recognize that we are going to see more cancer around the world. It's just going to increase and our systems will have to try and deal with that.

I want to shift gears a little bit because we are seeing a clear shift in where clinical trials are being done. Participation around the world has increased in clinical research. Tony, give us an idea of changes in clinical trial infrastructure that have occurred in your world and the importance they play in drug discovery and understanding about molecular profiling of cancer.

Dr. Mok: I am a lung cancer person, so I can speak mostly about lung cancer. About 10-15 years ago, I would have to say that the infrastructure for lung cancer research in Asia was actually quite minimal, in the sense that we were able to contribute some patients but we were never in the driver's seat, per se.

What changed the story was a few things. Number one is that we got organized. We worked together. Second is the story of the epidermal growth factor receptor (EGFR) mutation. It turned out that the EGFR mutation had a high incidence in our part of the world, such that if you want to do research on patients with this oncogenic driver, you have to become more heavily involved with the Asian countries. Being able to get together and organize, we were able to do a study that changed practice with the use of tyrosine-kinase inhibitors as the first-line therapy vs chemotherapy in patients with the mutation.[1]That gave us the opportunity to get even better, to be able to do high-quality studies that would build our infrastructure even more, and now we can carry on.

This has happened for 2 reasons. Number one is our ability to contribute to the international study, and the second is that by being able to contribute, we are going to make a difference. So, you can see that it has a snowball effect. At this year’s ASCO, there will be 2 major oral presentations on lung cancer coming from the Asian countries.[2,3]

Do Cancers Differ Around the World?

Dr. Marshall: Do you think that cancers are different around the world? In gastrointestinal cancers, the gastric cancer outcomes in Asia are so much better than they are in our country. Is it the surgeon or is it the biology? What is your take on that?

Dr. Mok: Two days ago, I gave a talk about lung cancer research in China. One slide I show is my picture and a picture of a chimpanzee, which look awfully alike, but the fact of the matter is that the genetic components between humans and chimps are about 98% similar. When you talk about East and West differences, we are probably talking about a few genetic mutations that are different. Although we look different, we differ by a very small number of genes.

Our job now is to find in cancer which genes are different. For example, we have the EGFR difference and the KRAS difference between the whole population; but after that, if you look at the oncogene, it's actually quite similar between the western and eastern populations. So, there is a lot to learn in the sense of which genes matter and which genes are different. There is a lot of research going on.

Dr. Kerr: This is fascinating. I agree with everything that you say, but in terms of us doing global studies, now there is a huge shift towards big pharmaceuticals, with trials having 50 patients from China, 50 from here, 50 from there, and they add up to a total of a couple thousand patients. Then we do some subgroup analyses, which turn out to be tiny.

Should we continue to do those types of studies because that is where we started to pick up these mutations in the early days? Does China, Asia, the Pacific Rim become a primary destination so that we have to do 2 sets of studies, one in the West and one in the East? Or do we still try to celebrate our genetic diversity so that we actually detect those subtle differences that might make a real difference?

Dr. Mok: There are 2 sides to consider. One is the scientific side. The multicountry involvement can be done, as long as you have translational research to know what you are looking for and to determine the genetic component that influences the outcome. The other side is regulation. For example, a certain drug may be no different between Japan and the rest of the world, but Japan will insist that you have to do your phase 1 studies. You have to do a pharmacokinetic study. It's regulatory, so the pharmaceutical companies have to adjust to that. It's not necessarily scientific, but it's the regulation.

Regulatory Hurdles and Headaches

Dr. Marshall: There has been a change, however, in some of this. We are sharing a lot more data. Certainly, in the United States, regulatory agencies over the past decade or so have embraced and accepted studies done outside the United States, as long as they meet certain criteria. Do you see a time when we might have a global approval?

Dr. Kerr: It is interesting. We could present a strong clinical and scientific rationale. We could present a strong rationale in terms of quality of data. We trust trials from China in a way that 20 years ago we might not have, for the reasons that you gave. But Tony is right: The regulatory boards are lagging well behind what we are doing scientifically.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are changing and improving. Health minister Tsung-Mei Cheng and colleagues are looking at the regulatory framework in China. Japan has always been somewhat inward-looking, not on the basis of rational science, but for sociopolitical and geographic reasons. In our lifetime, I suspect they won't change, but they should and they must. Perhaps we will start to promulgate approvals on the basis of science medicine, rather than geographic arbitrariness.

Dr. Mok: Gefitinib is still not available in the United States, despite it being approved in the rest of the world, so it is the acceptance of data. One of the reasons is that the FDA said that there were no American patients in the ad hoc study, so those data cannot be accepted.

The Way Ahead

Dr. Marshall: As the scientist driver, we have the vision; we can see a better world ahead. How do we get there? Are our international meetings, such as ASCO® and similar meetings around the world, having the needed impact on our populations and governments?

Dr. Kerr: Definitely, yes. Tony and I became friends because our societies wanted to collaborate. At ESMO last year, there were 600 Chinese medical oncologists at a major European meeting making an important intellectual contribution to it. There is no doubt that these international meetings are a melting pot -- a forum -- for us to come together, not like the old days when we would sit and listen and be lectured and hectored by key opinion leaders who were predominately from the West. Actually, now there is a much greater degree of synergy and participation and that is how we become pals. We start to collaborate.

The 3 of us are a triangle of collaboration. We are going to do work in vaccines together. Tony and I have some big plans to see how we can bring collaborative trial groups together and so on, and it can only occur through this collaboration.

Dr. Mok: I agree entirely. The international meetings give us the platform to exchange ideas and meet different people. It is not just the intellectual factor, it's broader: the idea of working together towards the same goal.

Dr. Marshall: Tony, David, thank you so much. This has been a great opportunity for us to get together -- not just to put the problems on the table, but actually to hear some solutions and some ways forward, as we are trying to globalize our oncology care. So, thanks very much.

I want to thank our audience, too, for joining us today for this Medscape Oncology Insights Roundtable. This is John Marshall reporting from ASCO® 2012.


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