Advanced Pancreatic Cancer and Molecular Testing


John Marshall, MD: We are making significant breakthroughs in understanding the biology of pancreatic adenocarcinoma and refining the use the use of combination chemotherapy. For the community oncologist, it’s critical to keep up with new research and understand the options being explored in clinical trials. In this Peer Exchange® discussion, I’m joined by an amazing panel of experts in the field of GI [gastrointestinal] oncology. Together we’re going to provide you with a perspective on the recent advances and what these mean to the care of your patients. I’m Dr John Marshall, chief of hematology and oncology at MedStar Georgetown University Hospital and a professor of medicine and oncology at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. I’m joined by, as I said, amazing folks:

Dr Edward Kim, an associate professor of medicine at the University of California, Davis and the chair of the UC Davis Pancreatic Cancer Research Incubator in Sacramento, California. Dr Kim, welcome.

Dr Paul Oberstein, an assistant director of the Pancreatic Cancer Center at NYU Langone Health’s Perlmutter Cancer Center in New York, New York. Welcome.

Dr Allyson Ocean, an associate professor of clinical medicine at Weill Cornell Medical College and a medical oncologist at New York-Presbyterian Hospital/Weill Cornell Medical Center, also in New York, New York. Welcome.

Dr. Shubham Pant, an associate professor in the Departments of Investigational Cancer Therapeutics and Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas. Welcome.

Paul, I’m going to pick on you first. Precision medicine is sort of here to stay. Pancreas cancer, to me, has been kind of a latecomer into this space. What’s your perspective on who should undergo molecular testing with pancreatic cancer—when, how, that sort of thing. Take it away.

Paul Oberstein, MD: I would say it’s true that we’re a latecomer to this game. There are very few active regimens that use the molecular testing to guide therapy, but that’s going to change. I think what we’ve seen when we look at large populations of patients is that there are actionable mutations that we pick up. The only way we’re going to find them is if we keep looking for them. Certainly, in the best settings where we’re collecting data, we recommend checking for somatic and germline mutations in almost every patient with pancreatic cancer.

John Marshall, MD: A piece of blood—send it for germline; a piece of tissue—send it for somatic.

Paul Oberstein, MD: Somatic, correct. Can we use names?

John Marshall, MD: Yes.

Paul Oberstein, MD: Something like Foundation Medicine analysis or another kind of complementary analysis.

John Marshall, MD: Let’s talk about that. One of the biggest problems I have with pancreas cancer is getting enough tissue for testing, particularly with local tumors using FNAs [fine-needle aspirations] and EUSs [endoscopic ultrasounds]. You guys do your own testing, I think.

Shubham Pant, MD: Yes.

John Marshall, MD: More and more, we partner with external folks to do these broader profiles. How critical is it? How much risk do I put that patient at to get enough tissue to do broad molecular testing?

Shubham Pant, MD: The molecular testing is, exactly as Paul said, here to stay. The issue in pancreatic cancer is that you don’t really know whom to test. Do you test the 1 who’s got 10 liver lesions? Do you test the 1 who has lung-only metastases? There are really no data to guide you. Do you test the 1 who got 2 months of FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin] and progressed? Do you test the 1 who got 8 months of FOLFIRINOX and did not progress? It’s kind of all over the place. It’s really muddy. It’s hard to find somebody we look at and say, “You know what, this guy’s got lung-only metastases, and I definitely should test this because they could come up with KRAS mutations also.”

The issue in pancreatic cancer, as we all know, is that about 90% have KRAS mutations, with 12 DVR [direct variable repeat] being the most common. Overwhelmingly we see these mutations come up. However, in the targeted therapy realm, I think about 20% to 25% can’t have targetable mutations. You can have MSI [microsatellite instability]—high 1%, you can have FGFR, or some fusions.

John Marshall, MD: Wait, I want to be sure I hear it. Paul is saying we should test everybody, right? Did I hear that?

Paul Oberstein, MD: I’m saying we should test everybody and share that information.

John Marshall, MD: Now we’re sharing, OK.

Paul Oberstein, MD: This is important because we don’t know.

John Marshall, MD: You’re talking about subsets of patients. Do you test everybody or not?

Paul Oberstein, MD: I agree with Paul there. Unless you test them, you won’t know. I think we really should. Right now, we don’t have enough data to know whom to test. I think germline—definitely, we should be testing everybody according to NCCN [National Comprehensive Cancer Network] Guidelines. When they come up, we should test for germline testing.

John Marshall, MD: Allyson, why are we doing that? Why are we doing germline testing on everybody for BRCA?

Allyson Ocean, MD: We didn’t used to do it.

John Marshall, MD: No. It’s new, right?

Allyson Ocean, MD: Right. It’s definitely new, and we now have data that show that if we can uncover a targeted mutation in this disease, it can lead to clinical trials. It will improve clinical trial enrollment, as well as data that just came out today regarding the BRCA mutation, uncovering that mutation, and having a therapeutic intervention because of that.

John Marshall, MD: Absolutely. We’re going to drill down on that in detail, of course.

Edward Kim, MD: One of the reasons for the change is that there is the potential to miss cases. If you go just on historical use of family history, there’s evidence now that you will miss a significant portion of patients.

John Marshall, MD: The more we look, the more we’re finding, right? We’re overturning a lot of our HPI [history and physical evaluation] and family history to actually find these folks. Back to you, Ed, on that. A lot of times, we’re doing testing, not so much in germline but somatic, and finding funky BRCA mutations. Are they all created equal? Or are some different from others?

Edward Kim, MD: We don’t know. We’re just getting information about the same germline mutations, and we’re needing to see whether this holds up for somatic, as well. I think the germline testing is most robust at this point, but there’s still a lot of explanation that needs to be done.

Transcript Edited for Clarity

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