Is Oncology Ready for 1000 Rare Diseases?
Is Oncology Ready for 1000 Rare Diseases?
Hello. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society of Medical Oncology. I would like to reflect a little on what, for me, was the take-home message from the recent American Society of Clinical Oncology (ASCO®) meeting. There were no major practice-changing trials in terms of my own interest, gastrointestinal cancer. Rather, I came away with a strong sense that cancer will increasingly be compartmentalized into 1000 rare diseases, each with its own phenotype, each with its own set of biomarkers, and each with its own portfolio of targeted therapies that will allow us as clinicians to be able to intervene rationally.
For me, it was almost a Damascene conversion. We've talked before about genetics, genomics, and the science underpinning medicine, but there was a real sense at this ASCO® meeting that it is really starting to bite. I picked up a recent fascinating article in the Annals of Oncology by Kay and colleagues from Queen's University Cancer Research Institute in Kingston, Canada. Some time ago, they made a survey of a variety of different randomized trials from 1975 to 2004 on breast, colorectal, and non-small cell lung cancer. They catalogued a variety of different metrics -- trial size, who funded the study, etc. Now, they have undertaken the same review, but this time for the period from 2005 to 2009. The 137 eligible randomized clinical trials that they found were from the 5 major journals that carry the majority of large randomized trials for cancer.
They really had some fascinating insights to offer. The number of randomized trials had increased from a median of 17 to 27 per year. The size of the trials had increased from a median patient recruitment in the old days of around 450 to an average trial size of 725 now, so it is a big step forward. The number of targeted therapies that were subject to clinical trials had risen from 4% to almost 30%. It is an incredible evolution but one that is based on knowledge. In a way, it doesn't surprise us, given the way that the pharmaceutical industry has adapted to using modern science and biomarker-driven studies. Of the 137 trials that were analyzed, almost 60% had biomarkers that were intimately involved in patient selection, stratification, and so on.
This is interesting. If we are to consider cancer 1000 rare diseases, it heralds a huge change in the clinical development pathways for the drugs that we use, instead of the conventional phase 1, phase 2, possibly randomized phase 2, and a large confirmatory phase 3 trial, taking many years with thousands of patients, and spending a billion dollars or whatever the latest guesstimate is. A significant example is crizotinib. We're seeing drugs going to the US Food and Drug Administration at the end of randomized phase 2 trials with a high chance of leaping the regulatory hurdles.
This presents a challenge to the clinical community. How do we find the space? How do we design the studies that allow us to bring each of these new drugs in? If we take a simplistic approach, it's a single drug for a single pathway. But already we are seeing combinations of targeted drugs yielding better responses, so we have the whole interesting mathematics as to how we combine different drugs in different ways.
Because of safety, we will see a huge increase in the number of phase 4 or postregulatory surveillance studies being undertaken. So this is a very interesting challenge. I felt that it was an almost Damascene conversion that this sense of personalized medicine is here to stay, but the proof of the pudding is in this very nice small paper by Kay looking as to how things have modified and moved forward. We must continually adapt as oncologists in how we think of trial design and what we think the regulatory hurdles might be to get a drug approved and on to those mean oncology streets.
Hello. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society of Medical Oncology. I would like to reflect a little on what, for me, was the take-home message from the recent American Society of Clinical Oncology (ASCO®) meeting. There were no major practice-changing trials in terms of my own interest, gastrointestinal cancer. Rather, I came away with a strong sense that cancer will increasingly be compartmentalized into 1000 rare diseases, each with its own phenotype, each with its own set of biomarkers, and each with its own portfolio of targeted therapies that will allow us as clinicians to be able to intervene rationally.
For me, it was almost a Damascene conversion. We've talked before about genetics, genomics, and the science underpinning medicine, but there was a real sense at this ASCO® meeting that it is really starting to bite. I picked up a recent fascinating article in the Annals of Oncology by Kay and colleagues from Queen's University Cancer Research Institute in Kingston, Canada. Some time ago, they made a survey of a variety of different randomized trials from 1975 to 2004 on breast, colorectal, and non-small cell lung cancer. They catalogued a variety of different metrics -- trial size, who funded the study, etc. Now, they have undertaken the same review, but this time for the period from 2005 to 2009. The 137 eligible randomized clinical trials that they found were from the 5 major journals that carry the majority of large randomized trials for cancer.
They really had some fascinating insights to offer. The number of randomized trials had increased from a median of 17 to 27 per year. The size of the trials had increased from a median patient recruitment in the old days of around 450 to an average trial size of 725 now, so it is a big step forward. The number of targeted therapies that were subject to clinical trials had risen from 4% to almost 30%. It is an incredible evolution but one that is based on knowledge. In a way, it doesn't surprise us, given the way that the pharmaceutical industry has adapted to using modern science and biomarker-driven studies. Of the 137 trials that were analyzed, almost 60% had biomarkers that were intimately involved in patient selection, stratification, and so on.
This is interesting. If we are to consider cancer 1000 rare diseases, it heralds a huge change in the clinical development pathways for the drugs that we use, instead of the conventional phase 1, phase 2, possibly randomized phase 2, and a large confirmatory phase 3 trial, taking many years with thousands of patients, and spending a billion dollars or whatever the latest guesstimate is. A significant example is crizotinib. We're seeing drugs going to the US Food and Drug Administration at the end of randomized phase 2 trials with a high chance of leaping the regulatory hurdles.
This presents a challenge to the clinical community. How do we find the space? How do we design the studies that allow us to bring each of these new drugs in? If we take a simplistic approach, it's a single drug for a single pathway. But already we are seeing combinations of targeted drugs yielding better responses, so we have the whole interesting mathematics as to how we combine different drugs in different ways.
Because of safety, we will see a huge increase in the number of phase 4 or postregulatory surveillance studies being undertaken. So this is a very interesting challenge. I felt that it was an almost Damascene conversion that this sense of personalized medicine is here to stay, but the proof of the pudding is in this very nice small paper by Kay looking as to how things have modified and moved forward. We must continually adapt as oncologists in how we think of trial design and what we think the regulatory hurdles might be to get a drug approved and on to those mean oncology streets.
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