The Future of Advanced Pancreatic Cancer

Transcript:

John L. Marshall, MD: This is a free-for-all. Does anybody have a cool study that they want to pitch? You’ve got a nationwide, worldwide audience. Is there anything out there that you really think they should go on or steer toward?

Tanios S. Bekaii-Saab, MD: Well, I think that PARP inhibitors are making a good segue into this disease.

John L. Marshall, MD: Find the HRD patients and get them on those studies.

Tanios S. Bekaii-Saab, MD: Absolutely. There are a few PARP inhibitors that seem to continue to move forward in oncology but also in pancreatic cancer now—olaparib, rucaparib, talazoparib, and others as well. Veliparib has been relatively disappointing. The whole premise of developing veliparib was…

John L. Marshall, MD: So, if there is a PARP inhibitor study, get on it?

Tanios S. Bekaii-Saab, MD: Yes, a good one.

George P. Kim, MD: But let me remind everybody that it’s what, 11%? So, obviously…

John L. Marshall, MD: It’s not for everybody.

Tanios S. Bekaii-Saab, MD: Well, I would say 3% to 4% or 5% or 8% or 10%. It’s all over the place. Nonetheless, anything above 1% is worth looking for. The difference is crazy.

John L. Marshall, MD: Are there any other studies out there that you think are cool going forward?

George P. Kim, MD: Abraxane (nab-paclitaxel) and gemcitabine in the adjuvant setting. That’s going to be really interesting, especially with...

Tanios S. Bekaii-Saab, MD: APACT.

George P. Kim, MD: Today, how are we going to decide which treatment to use? Are the numbers going to be similar? Again, patient selection. I think that’s going to change how we treat patients, especially in the adjuvant setting.

Tanios S. Bekaii-Saab, MD: And it’s an international study, unlike, again, the FOLFIRINOX studies, which have consistently been French studies. The nab-paclitaxel studies have been more international, so there are certain variabilities in how you can interpret or cross-compare.

Eileen M. O’Reilly, MD: The adjuvant trial had a significant Canadian contribution.

Tanios S. Bekaii-Saab, MD: Yes.

John L. Marshall, MD: We’re throwing everything at immunotherapy plus whatever else you have in your garage. Do you see some promise or some hope? Or do we need to let this mature a bit before moving forward?

Eileen M. O’Reilly, MD: I do. I think that if there’s a path forward for immunotherapy for the broad patient population, it’s going to be through combining up front with chemotherapy and then maybe deescalating. There’s a nice example. The Parker Institute consortium is looking at CD40-agonistic antibodies and checkpoints combined with chemotherapy. I know there are several examples of other studies. The CSF1R data in pancreatic cancer, in combination with nivolumab, look interesting. That’s being explored in a second-line, randomized phase II study. The MORPHEUS platform is multiple arms. We’ll get some hints. We’ll learn.

Tanios S. Bekaii-Saab, MD: Yes. It’s all about understanding your drivers and your microenvironment—your immunosuppressive versus your immunostimulatory drivers. You want to suppress the bad and enhance the good. Checkpoint inhibitors, by themselves, even if you pile up on the checkpoint inhibitors, are not going to do it. The CSF1Rs are actually very interesting because they bring down those bad macrophages and essentially allow for those good macrophages.

I agree with Eileen. The challenge remains the same. All these manipulations will depend on whether you can break that barrier. But again, be very careful about how you do it. You will need a chemotherapy backbone.

George P. Kim, MD: The barrier is the stroma. You’ve got to attack the stroma.

Tanios S. Bekaii-Saab, MD: Part of the stroma. It’s only part of the stroma.

George P. Kim, MD: And I hope it will be done in combinations. So that’s where I think we’re headed.

Tanios S. Bekaii-Saab, MD: It’s only part of the stroma, right? It’s the outside the stroma.

John L. Marshall, MD: Choose whether or not you want to give leucovorin. Decide whether the stroma is a positive or a negative. But the big picture here is that breakthrough, practice-changing data in the adjuvant setting and additional data in the metastatic setting give us some more help in determining how to best manage that patient. I think you have done a terrific job of summarizing where we are and where we are headed in the next phase. There is hope. We have to keep working on this so that we do not stay as frustrated as we are, going forward.

This has been extremely informative. Before we end, I’d like to offer each one of our panelists a moment to share a final thought. George, you get the floor first.

George P. Kim, MD: Sequencing. We’ve got regimens that we can use to sequence patients—nab-paclitaxel/gemcitabine followed by nal-IRI (liposomal irinotecan). That’s how we select which drug regimen we can use. If we go with FOLFIRINOX, there is a lot of management. Then we don’t know what to do in the second-line setting. We have to go back to the basics. That’s what we have in June of 2018. We’ve got to think about sequencing. We’ve got to think about the FDA approved drugs—the Category 1 recommended regimens—and all the research.

John L. Marshall, MD: You have to be a smart-balanced oncologist. Dr. Mody?

Kabir Mody, MD: I would say that a multidisciplinary approach to potentially resectable patients is important. Give them all the options and all the treatment up front. The pancreatic cancer community has done a fantastic job, patients included, in raising awareness for this disease. Get patients into trials whenever possible, wherever they are around you, for whatever is practical for the patient to do. There are a lot of options, and we have immunotherapy. We’ve recognized the need to address this in a very comprehensive way—in a multifaceted way, not just a 1-drug way. Those agents and a multitude of agents are coming. I think there’s a lot of hope.

John L. Marshall, MD: Dr. O’Reilly?

Eileen M. O’Reilly, MD: I completely echo what George and Kabir have said. I endorse all of that and would like to make 2 additional points. I think access to new agents is important. We’ve probably gotten to the ceiling with where we are with current cytotoxics. And also, an increased focus on early detection. That’s actually where we’ll make the biggest impact on this disease. That’s a challenge.

John L. Marshall, MD: Tanios?

Tanios S. Bekaii-Saab, MD: I echo everything that was said. The most important message, when you think about your treatment options, is: Think about your patient. Don’t think about a scan or a biochemical marker or any other marker. Ultimately, we want to make sure that our patients have the best quality of life and quantity of life. It takes a lot of balance. The second point I want to make—done with the leucovorin.

John L. Marshall, MD: Thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope that you found this Peer Exchange^® discussion to be useful and informative.

Transcript Edited for Clarity