What Will It Take to Maximize Personalized Medicine?
What Will It Take to Maximize Personalized Medicine?
Maurie L. Markman, MD: Hello. I am Maurie Markman, Professor of Medicine and Vice President for Clinical Research at the University of Texas MD Anderson Cancer Center in Houston, Texas. It is my pleasure to welcome you to Medscape Oncology Insights on Personalized Medicine.
I am joined today by Dr. Richard Schilsky, Professor of Medicine and Section Chief of Hematology/Oncology at the University of Chicago Medical Center and past President of ASCO [American Society of Clinical Oncology].
To begin this discussion, I would like to briefly read from a wonderful paper that Dr. Schilsky wrote -- actually in his Presidential Address at ASCO:
What will it take to do this personalized medicine in oncology? A biospecimen from every patient, a validated assay run in a CLIA [Clinical Laboratory Improvement Amendment]-certified laboratory with acceptable turnaround time, a drug that hits the target, a regulatory system willing to approve drugs and companion diagnostics with greater flexibility, reimbursement and regulatory incentives to develop molecular diagnostics, a drug industry willing to trade widespread short-term drug use for chronic therapy in more limited populations, and, very importantly, doctors and patients who are willing and able to participate in clinical trials.
Rich, I couldn't imagine it being said better. How do we do this?
Richard L. Schilsky, MD: I tried to lay out the blueprint last year in my Presidential Address, and it's complicated. We need all of those pieces in order for it to work. Most importantly we need more research. I think it's becoming increasingly clear that if we really understand the drug targets and we can identify really important targets that really drive a tumor and we have a really good inhibitor, wonderful things can happen.
We saw an example of it just this year at ASCO in the plenary session with a new drug that hits a target that occurs in only 5% of patients with non-small-cell lung cancer. When the target is present and the drug is given at an appropriate dose, those tumors shrink; it's really a remarkable finding.
What we need are both doctors and patients to be more mindful of the importance of using the tissue for more than just routine diagnostic purposes. Patients have to insist that their tissue be preserved for more molecular diagnostic testing as it becomes available. The tests have to be reliable like any test we do on a patient. If the test is not done in a reliable way, if it's not an analytically validated test, if it's not done in the laboratory with appropriate methods and controls, we can get erroneous information, which could be as bad for a patient as not doing the test at all. You have to have a good test done in a good lab. We have to have incentives for test developers to actually develop these diagnostic tests. The reimbursement for these tests is far less than it is for drug therapy, and yet the tests can not only direct the treatment so that we give more effective treatment for patients but they can actually reduce the overall costs of care by avoiding the use of treatments that are not likely to be effective. We need the payers to recognize that even a test that may appear to be expensive overall can reduce healthcare costs.
Importantly, at the end of the day we still need doctors and patients to participate in clinical trials because it's only through that mechanism that we'll continue to get the definitive data that we need to inform both clinical and regulatory decisions.
Dr. Markman: There are a couple of follow-up questions. With the timing and where we are today in our society, there is discussion about healthcare reform and about comparative effectiveness research. How do you see those 2 things perhaps playing out in the personalized medicine world?
Dr. Schilsky: Those are big topics. I think comparative effectiveness on the surface addresses issues that doctors and patients want to know about every day in their routine encounters. There are 2 treatments that are available for treating a specific kind of cancer; which one is better? They may never have been compared head to head, but if you start to delve into that a little bit further, what you'd also like to know is not necessarily which one is better but which one is better for the patient sitting in front of me. That's where if you begin to do some of the large simple trials that advocates of comparative effectiveness research claim are going to be useful, if you couple those trials with collecting biospecimens so you can compare regimen A, a known effective regimen, to regimen B, another known effective regimen, collect the biospecimens and ultimately figure out regimen A is really good for patients who have these tumor characteristics and regimen B is really good for patients with those tumor characteristics, then we have a much more informed way of guiding therapy for patients.
Dr. Markman: Potentially large trials where those questions are looked at prospectively become very valid. Not just after the fact trying to figure that it worked.
Dr. Schilsky: Ultimately, if you really want to prove the point, you need to do a prospective trial. Those are complicated and take time to do, but at the end of the day that's the only way we'll get the definitive data. I still think that we can get a lot of value from the so-called prospective-retrospective kinds of analyses where we do a trial, we collect the specimens, we decide right up front what are the biological questions we want to ask with those specimens. Then we ask them after the outcomes of the patients are already known. That's the prospective-retrospective part, and that's how all the data about KRAS mutation and cetuximab were developed.
Dr. Markman: You didn't need to do a prospective trial for that. You were able to collect the data afterwards. I think that's very important. The last question is another topic that you've been very involved in. Both of us have been very involved in NCI [National Cancer Institute] efforts, the cooperative group efforts, you in particular with a Chair of CALGB [Cancer and Leukemia Group B], a recent report suggesting that there needs to be really an overhaul. Considering the extraordinary importance of the NCI, the cooperative groups in our research, in personalized medicine how do you see the future for that?
Dr. Schilsky: It's easy for me to talk about this now that I'm a retired cooperative chair after 15 years as CALGB Chair, but I think fundamentally everybody acknowledges, even the cooperative group leaders acknowledge, that the groups need to become more efficient. We need to launch trials much more quickly, we need to complete them more quickly, and we need to get the answers that patients and doctors want to know as soon as possible. Our ability to engage with pharmaceutical companies that are increasingly moving the most innovative trials and most exciting drugs offshore to other countries so our American patients are not even getting access to them in a timely fashion really depends on us getting trials up and running quickly.
The NCI, through the Operational Efficiency Working Group, is developing new targets for time to launch of protocols. I think we have a clear understanding of why it takes so long, and it should not be that difficult to fix it. We need to streamline the review process, we need to get better protocol tracking so we know exactly where in the queue a protocol stands, and, importantly, the investigators who are working on these protocols with us in the cooperative groups need to have some protective time to actually devote to writing these protocols and getting them done as quickly as possible.
I think change is inevitable in the cooperative group program. I think there will be likely some consolidation of some aspects of the cooperative groups. That may be good to eliminate redundancy, but I think it's important that we also preserve some room for competition and different perspectives and alternative trial designs to be launched. I think the cooperative group program is vital to advancing all of our goals in cancer research. There are trials that are done by the groups that simply will not be done by industry but have the potential to answer very important questions. We need to be sure that we have a very robust, publically funded clinical trial system in this country, and it means everybody's going to have to work together to achieve that.
Dr. Markman: Well stated. I want to thank Dr. Richard Schilsky for joining me for this Medscape Peer-to-Peer discussion on personalized medicine. Thanks for listening. This is Maurie Markman at ASCO 2010.
Maurie L. Markman, MD: Hello. I am Maurie Markman, Professor of Medicine and Vice President for Clinical Research at the University of Texas MD Anderson Cancer Center in Houston, Texas. It is my pleasure to welcome you to Medscape Oncology Insights on Personalized Medicine.
I am joined today by Dr. Richard Schilsky, Professor of Medicine and Section Chief of Hematology/Oncology at the University of Chicago Medical Center and past President of ASCO [American Society of Clinical Oncology].
To begin this discussion, I would like to briefly read from a wonderful paper that Dr. Schilsky wrote -- actually in his Presidential Address at ASCO:
What will it take to do this personalized medicine in oncology? A biospecimen from every patient, a validated assay run in a CLIA [Clinical Laboratory Improvement Amendment]-certified laboratory with acceptable turnaround time, a drug that hits the target, a regulatory system willing to approve drugs and companion diagnostics with greater flexibility, reimbursement and regulatory incentives to develop molecular diagnostics, a drug industry willing to trade widespread short-term drug use for chronic therapy in more limited populations, and, very importantly, doctors and patients who are willing and able to participate in clinical trials.
Rich, I couldn't imagine it being said better. How do we do this?
Richard L. Schilsky, MD: I tried to lay out the blueprint last year in my Presidential Address, and it's complicated. We need all of those pieces in order for it to work. Most importantly we need more research. I think it's becoming increasingly clear that if we really understand the drug targets and we can identify really important targets that really drive a tumor and we have a really good inhibitor, wonderful things can happen.
We saw an example of it just this year at ASCO in the plenary session with a new drug that hits a target that occurs in only 5% of patients with non-small-cell lung cancer. When the target is present and the drug is given at an appropriate dose, those tumors shrink; it's really a remarkable finding.
What we need are both doctors and patients to be more mindful of the importance of using the tissue for more than just routine diagnostic purposes. Patients have to insist that their tissue be preserved for more molecular diagnostic testing as it becomes available. The tests have to be reliable like any test we do on a patient. If the test is not done in a reliable way, if it's not an analytically validated test, if it's not done in the laboratory with appropriate methods and controls, we can get erroneous information, which could be as bad for a patient as not doing the test at all. You have to have a good test done in a good lab. We have to have incentives for test developers to actually develop these diagnostic tests. The reimbursement for these tests is far less than it is for drug therapy, and yet the tests can not only direct the treatment so that we give more effective treatment for patients but they can actually reduce the overall costs of care by avoiding the use of treatments that are not likely to be effective. We need the payers to recognize that even a test that may appear to be expensive overall can reduce healthcare costs.
Importantly, at the end of the day we still need doctors and patients to participate in clinical trials because it's only through that mechanism that we'll continue to get the definitive data that we need to inform both clinical and regulatory decisions.
Dr. Markman: There are a couple of follow-up questions. With the timing and where we are today in our society, there is discussion about healthcare reform and about comparative effectiveness research. How do you see those 2 things perhaps playing out in the personalized medicine world?
Dr. Schilsky: Those are big topics. I think comparative effectiveness on the surface addresses issues that doctors and patients want to know about every day in their routine encounters. There are 2 treatments that are available for treating a specific kind of cancer; which one is better? They may never have been compared head to head, but if you start to delve into that a little bit further, what you'd also like to know is not necessarily which one is better but which one is better for the patient sitting in front of me. That's where if you begin to do some of the large simple trials that advocates of comparative effectiveness research claim are going to be useful, if you couple those trials with collecting biospecimens so you can compare regimen A, a known effective regimen, to regimen B, another known effective regimen, collect the biospecimens and ultimately figure out regimen A is really good for patients who have these tumor characteristics and regimen B is really good for patients with those tumor characteristics, then we have a much more informed way of guiding therapy for patients.
Dr. Markman: Potentially large trials where those questions are looked at prospectively become very valid. Not just after the fact trying to figure that it worked.
Dr. Schilsky: Ultimately, if you really want to prove the point, you need to do a prospective trial. Those are complicated and take time to do, but at the end of the day that's the only way we'll get the definitive data. I still think that we can get a lot of value from the so-called prospective-retrospective kinds of analyses where we do a trial, we collect the specimens, we decide right up front what are the biological questions we want to ask with those specimens. Then we ask them after the outcomes of the patients are already known. That's the prospective-retrospective part, and that's how all the data about KRAS mutation and cetuximab were developed.
Dr. Markman: You didn't need to do a prospective trial for that. You were able to collect the data afterwards. I think that's very important. The last question is another topic that you've been very involved in. Both of us have been very involved in NCI [National Cancer Institute] efforts, the cooperative group efforts, you in particular with a Chair of CALGB [Cancer and Leukemia Group B], a recent report suggesting that there needs to be really an overhaul. Considering the extraordinary importance of the NCI, the cooperative groups in our research, in personalized medicine how do you see the future for that?
Dr. Schilsky: It's easy for me to talk about this now that I'm a retired cooperative chair after 15 years as CALGB Chair, but I think fundamentally everybody acknowledges, even the cooperative group leaders acknowledge, that the groups need to become more efficient. We need to launch trials much more quickly, we need to complete them more quickly, and we need to get the answers that patients and doctors want to know as soon as possible. Our ability to engage with pharmaceutical companies that are increasingly moving the most innovative trials and most exciting drugs offshore to other countries so our American patients are not even getting access to them in a timely fashion really depends on us getting trials up and running quickly.
The NCI, through the Operational Efficiency Working Group, is developing new targets for time to launch of protocols. I think we have a clear understanding of why it takes so long, and it should not be that difficult to fix it. We need to streamline the review process, we need to get better protocol tracking so we know exactly where in the queue a protocol stands, and, importantly, the investigators who are working on these protocols with us in the cooperative groups need to have some protective time to actually devote to writing these protocols and getting them done as quickly as possible.
I think change is inevitable in the cooperative group program. I think there will be likely some consolidation of some aspects of the cooperative groups. That may be good to eliminate redundancy, but I think it's important that we also preserve some room for competition and different perspectives and alternative trial designs to be launched. I think the cooperative group program is vital to advancing all of our goals in cancer research. There are trials that are done by the groups that simply will not be done by industry but have the potential to answer very important questions. We need to be sure that we have a very robust, publically funded clinical trial system in this country, and it means everybody's going to have to work together to achieve that.
Dr. Markman: Well stated. I want to thank Dr. Richard Schilsky for joining me for this Medscape Peer-to-Peer discussion on personalized medicine. Thanks for listening. This is Maurie Markman at ASCO 2010.
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