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Pancreatic Cancer: Where to Next?

Insights From:Philip A. Philip, MD, Karmanos Cancer Center; Tanios Bekaii-Saab, MD, Mayo Clinic
Published: Wednesday, Sep 21, 2016


Transcript:

Philip A. Philip, MD:
Clinical trials in pancreatic cancer have been famous for being negative. In fact, if we look at the major clinical trials that have resulted in drugs that we brought to the clinic, I would count maybe five clinical trials that prospectively tested a drug or a drug combination that led to either an approval by the FDA or an adoption in our daily practices. And opposite to that, there were many clinical phase III trials, with thousands of patients and millions of dollars in costs, that were negative.

At this point in time, if we’re thinking of what is the next clinical trial and what to do, if we can find a way of moving into immunotherapy—and if we find the right targets or the right way of doing it and having the right drugs being together—that will be an interesting area to do. Because if it’s working in other tumor types, it’s a shame to think that it’s not going to work somehow in pancreatic cancer. So, that may be one area which I would be interested in.

Another area which has been gaining a lot of attention is trying to do clinical trials in patients who have tumors that have some defects in DNA repair. Basically, these are patients who have tumors that cannot handle the insult they get with chemotherapy, like platinum compounds that damage the DNA. And our cells can immediately fix that damage. But there are tumors that cannot do that, which is great for me, because if I identify a patient who has such a tumor, then I can go after it with some newer drugs; for example, the PARP inhibitors, etc. So, that’s another area. I can tell you that that area has already been very busy with clinical trials doing that—but it would be interesting. If I find drugs that can target the stroma, the cells, the material, and everything which is surrounding the tumor cells, then, again, that would be another set of clinical trials. But there is a clinical trial now looking at PEGylated hyaluronidase, the PEGPH20 which is combined with chemotherapy. Those trials have already started, so that’s an area which is currently ongoing.

The bottom line is that we need some good biology to drive our clinical trials. We’ve done a lot of clinical trials on an empirical basis and they turned out to be negative. That really challenges, a lot of times, our statements that every patient should go on a clinical trial, because people and patients will say, “We read about clinical trials, but a lot of times they were negative.” So, to counter that, we have to do clinical trials that are really based on good science, a good chance of the trial being positive, and not jumping into what we call phase III trials with 600 patients, but rather doing small clinical trials that show some improvement that is worth taking into a clinical trial.

Just to give an example: recently, there was an article on a drug that targets macrophages. Specifically, they target a receptor, CCR2, which is a macrophage. So, these are bad cells. Macrophages are the bad cells that populate a tumor. And with all the bad things about drug resistance, they don’t help us to kill the tumor cells, etc. They also help the tumor to progress. There is a drug that has been tested recently in a very pilot setting—like single-arm, not randomized—and it showed that it can improve the outcome of patients’ locally-advanced unresectable disease. These are things which now will go into the second phase, which is a randomized phase II trial. So, we need to have some good initial read on activity before we jump on randomized trials, because we owe it to our patients. We have to do the good trials with drugs that have a good chance of working rather than jump into clinical trials.

Transcript Edited for Clarity
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Transcript:

Philip A. Philip, MD:
Clinical trials in pancreatic cancer have been famous for being negative. In fact, if we look at the major clinical trials that have resulted in drugs that we brought to the clinic, I would count maybe five clinical trials that prospectively tested a drug or a drug combination that led to either an approval by the FDA or an adoption in our daily practices. And opposite to that, there were many clinical phase III trials, with thousands of patients and millions of dollars in costs, that were negative.

At this point in time, if we’re thinking of what is the next clinical trial and what to do, if we can find a way of moving into immunotherapy—and if we find the right targets or the right way of doing it and having the right drugs being together—that will be an interesting area to do. Because if it’s working in other tumor types, it’s a shame to think that it’s not going to work somehow in pancreatic cancer. So, that may be one area which I would be interested in.

Another area which has been gaining a lot of attention is trying to do clinical trials in patients who have tumors that have some defects in DNA repair. Basically, these are patients who have tumors that cannot handle the insult they get with chemotherapy, like platinum compounds that damage the DNA. And our cells can immediately fix that damage. But there are tumors that cannot do that, which is great for me, because if I identify a patient who has such a tumor, then I can go after it with some newer drugs; for example, the PARP inhibitors, etc. So, that’s another area. I can tell you that that area has already been very busy with clinical trials doing that—but it would be interesting. If I find drugs that can target the stroma, the cells, the material, and everything which is surrounding the tumor cells, then, again, that would be another set of clinical trials. But there is a clinical trial now looking at PEGylated hyaluronidase, the PEGPH20 which is combined with chemotherapy. Those trials have already started, so that’s an area which is currently ongoing.

The bottom line is that we need some good biology to drive our clinical trials. We’ve done a lot of clinical trials on an empirical basis and they turned out to be negative. That really challenges, a lot of times, our statements that every patient should go on a clinical trial, because people and patients will say, “We read about clinical trials, but a lot of times they were negative.” So, to counter that, we have to do clinical trials that are really based on good science, a good chance of the trial being positive, and not jumping into what we call phase III trials with 600 patients, but rather doing small clinical trials that show some improvement that is worth taking into a clinical trial.

Just to give an example: recently, there was an article on a drug that targets macrophages. Specifically, they target a receptor, CCR2, which is a macrophage. So, these are bad cells. Macrophages are the bad cells that populate a tumor. And with all the bad things about drug resistance, they don’t help us to kill the tumor cells, etc. They also help the tumor to progress. There is a drug that has been tested recently in a very pilot setting—like single-arm, not randomized—and it showed that it can improve the outcome of patients’ locally-advanced unresectable disease. These are things which now will go into the second phase, which is a randomized phase II trial. So, we need to have some good initial read on activity before we jump on randomized trials, because we owe it to our patients. We have to do the good trials with drugs that have a good chance of working rather than jump into clinical trials.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Integrating Novel Targeted Treatment Strategies to Advance Pancreatic Cancer CareNov 30, 20181.0
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