Progress and Promise in Advanced Pancreatic Cancer - Episode 11

Molecular Profiling in Pancreatic Cancer

Transcript:Johanna Bendell, MD: Also with this data, we keep thinking of microsatellite instability in colon cancer, but we keep forgetting that there’s other cancers that are involved that have microsatellite instability, including pancreas and gastric cancer. It really starts to make you think the way that we’re treating all of our patients with cancer is changing. And the importance of molecular testing. Philip, what do you think; does this change your mind? Does this make you think for pancreas cancer that I should be looking for microsatellite instability, or BRCA, or things like that?

Philip A. Philip, MD, PhD, FRCP: With microsatellite instability, the frequency in all-comers would be 1% or so. So, it’s a very low percentage. The question is, are we recommending to our colleagues to do the testing, routinely, just for microsatellite instability? Are there any other additional results that will impact our treatments? I have to admit that I do it routinely in our patients, and I do that usually in a commercial lab. We don’t do it in-house. I know at Dana-Farber Cancer Institute, maybe they do it in-house. They used to do it. So, basically, if you ask me about the last 100 patients who I’ve done the test on, did I change treatments? Did I do something different? I can tell you, that with the exception of BRCA2 mutation, which may impact the use of platinum compounds or sending a patient to a PARP inhibitor study, you see lots and lots of p53 mutations, p16 mutations, and obviously KRAS. But what do you do with those mutations? And you might see the odd HER2/neu. But, certainly, if I want to tell patients I will do the test, and I’m going to change the treatment, or plan the treatment, that is not going to happen 98%, 97% of the time; it doesn’t.

Now, at this time, we have BRCA2. We can chase the microsatellite instability based on what we know, but that’s limited. There are other mutations for which we don’t know what they are, what they do. And we have a robust phase I program, which is nowhere near yours, but, obviously, we can benefit from some of the drugs they have for us to use. But that’s also a question for you, maybe for pancreatic and other cancers. How much do you find it beneficial to do since you are also leading the phase I effort in GI? Now, I’m asking the question. I’m the moderator.

Johanna Bendell, MD: I’ll answer your question very quickly. I think for us, with access to the clinical trials that we have for the new agents, certainly we’re doing a lot more molecular profiling across the board, including pancreas cancer patients. So far, not many of the pancreas cancer patients have benefitted from this testing. But I think as we do more and more, and we have more agents that are being developed…Certainly there are a number of new drugs that are in phase I now that are looking at pancreatic cancer patients; people looking at vaccines against CA 19-9, specific immunotherapies that are meant to target pancreatic cancer cells, other targeted agents, as well. So, I think that in the context of you getting a patient to a clinical trial, I think it makes a lot of sense.

Caio Rocha Lima, MD: I’m going to answer the question as well, even though he’s not even asking me. I think it can direct to the appropriate phase I trial. We are moving on for the cytotoxic base phase I trials, not only phase I trials, treatment in cancer, in general. And I think that targeting a potential driver mutation should start in phase I. So, most of the phase I trials now are in a rigid patient population. We are moving on from the histology base, phase Ibs, to actually a mutation-based or driver mutation-based phase I trial. Having that panel in mind helped me to think about, not the first- and second-line that we have today, but the third-line down the line for the patient that still has good organ function and good performance status.

George P. Kim, MD: I want to jump in here and advertise something for PanCAN because there was a really good presentation last night from PanCAN. They have a program where they’ll do some molecular analyses of the tumor. It’s called, Know Your Tumor, and that’s a really good way for patients to have the molecular marker work done. Everybody knows PanCAN is the advocacy group that’s for pancreatic cancer. They’ve done a tremendous job, and they have this opportunity out there. They’re working with ProThera, a company in the DC area. We need to direct our patients to this. I know we all have in-house ways of looking at genetic profiling, but we owe it to patients and to PanCAN, because they’re going to spend I think around $200 million in the next several years trying to get this program up and running, and trying to get the right trials. So, I’m just trying to advertise that for you.

Johanna Bendell, MD: Great resource.

Transcript Edited for Clarity