Drivers of discovery
Despite the challenges of high development costs, payers' willingness to reimburse, and sharp variations in patient access,
the science of cancer continues to improve. What are the most important advances that will enhance treatment options for patients?
Paterson: The application of anti-cancer stem cell therapy to treat metastatic cancer is a field that is evolving rapidly. Bob Weinberg
of MIT, one of the founders of my company, has developed a process for identifying a stable population of cancer stem cells
that in turn makes it possible to test a large number of drugs to find the few with sufficient potency and selectivity to
limit the cancer stem cells' capacity to reproduce the cancer through the body. These drugs focus on fighting the cancerous
stem cells rather than the bulk of the tumor itself. By mid-2013 we will have three clinical test programs underway—one is
for mesothelioma—that will try to pair these drugs with conventional chemotherapeutic treatment regimens designed to attack
the tumor. The interaction between cancer stem cells and tumor cells is fascinating and hopefully this work will guide our
understanding of how these two lines interact in pulling the trigger on metastases. This is important to cancer survival rates,
as most of the progress in cancer treatment to date has been in eliminating cancer at the early stage; once a tumor becomes
metastatic, we are not so good at stopping it.
Martell: The success rate for oncology drug development has been stuck for years at about five percent. A contributing factor may
be lack of predictability of pre-clinical efficacy models. For example, we rely on killing tumors in animal populations, which
may not be the best predictors of outcomes in humans. So finding novel ways of screening drugs that don't depend on tumor
shrinkage may improve the odds, even though the naysayers will tell you that there is almost no example of an approved drug
that did not show this kind of effect.
Puente: Researchers are often bound by rigid definitions. I recall a case of a test drug for liver cancer in which the tumor was
actually decreasing but due to necrosis within the liver and inflammation in surrounding tissue, it looked as if the tumor
was progressing. Investigators had to pull the patients and ultimately the project because it was hard to identify the clean
result sought by regulators. When you confront real life problems like these, it's hard to chart a path forward to Phase III
and registration, which is of course what the drug company wants.
Stein: Novartis is looking closely at changes to the structure and execution of the clinical trials we fund. Why is it that in adult
oncology we get only a three to five percent enrollment rate, while pediatric medicine typically gets 80 percent? One thing
we have found is there is a huge harvest of data to be found in the molecular screening work conducted outside of the industry
and academic networks, mostly by private companies who specialize in testing. That information can certainly be useful in
framing our trial protocols around the most recruitment ready patients, regardless of location. Typically, we will have to
pay to access this information, as payers are reluctant to share the cost, but this will be less of a factor as the cost of
screening goes down—at some point in the near future, it will be more expensive to store the data than to pay for the test.