Metastatic Pancreatic Cancer Guideline Update

An interview with Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on "Metastatic Pancreatic Cancer: ASCO Guideline Update." This update covers new information on targeted therapies for metastatic pancreatic cancer. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines

Transcript

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Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org.

My name is Brittany Harvey, and today I'm interviewing Dr. Davendra Sohal from the University of Cincinnati, and Dr. Daniel Laheru from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-chairs on Metastatic Pancreatic Cancer, ASCO Guideline update. Thank you for being here, Dr. Sohal and Dr. Laheru.

Hi, Brittany. Thank you for inviting us.

Happy to be here. Thanks.

First, I'd like to note that ASCO takes great care in development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. But Doctor Sohal, do you have any relevant disclosures that are directly related to this guideline topic?

No, I do not have anything directly in conflict. Thank you.

And Dr. Laheru, do you have any relevant disclosures that are related to this guideline topic?

Thank you, Brittany. I do not either.

Great. Than delving into the guideline content, Dr. Laheru, can you tell us what prompted an update to this guideline?

Yeah, sure. So what has been seen in almost every cancer is that with careful understanding of the molecular alterations of individual cancers, that targeted therapies have been developed for almost every cancer. And so for pancreas cancer, we have not had an opportunity in the past to use targeted therapies. Because for pancreas cancer, many of the genetic alterations that are found in other cancers are not seen in pancreas cancer. And so the guidelines were updated based on new evidence of the use of certain targeted therapies for pancreas cancer.

Then Dr. Sohal, what are the key updates that were made to the recommendations in this guideline iteration?

So the key updates relate to the so-called targeted therapies, the genomic-driven therapies that have now come up with evidence that pertains to pancreatic cancer as well. The overarching update is that every patient with metastatic pancreatic cancer who is a candidate for treatment should have tumor or somatic, the so-called somatic genomic profiling, as well as germline genomic testing, because these can lead to treatment recommendations.

And those treatment recommendations include PD-1 checkpoint inhibitor therapies for microsat light instability high tumors, track the TRK fusion inhibitors, such as larotrectinib and entrectinib for track fusions in tumors. And PARP inhibitors, such as olaparib for germline BRCA1 or BRCA2 mutations to be used as maintenance therapy after stable disease on platinum-based therapy.

Then Dr. Laheru, can you speak to the importance of this guideline and how it will drive changes to clinical practice?

Yes. So as Dr. Sohal said, these specific genetic alterations, the mismatch repair deficiency, the use of PARP inhibitors for BRCA1, BRCA2 germline mutations or somatic mutations that are pathologically significant, and for the NTRK fusion transcripts, even though these mutations for pancreas cancer are quite unusual, less than 5%, for example, for NTRK fusion transcripts, 5% to 10% for BRCA1, BRCA2 germline mutations, and probably 1% or 2% for a mismatch repair deficient pancreas cancer, the committee felt that we should inform the larger cancer community that even though these mutations are uncommon, if they are found, they could be very important for individual treatment for pancreas cancer.

And so this is why we really felt that it was time to provide an update, because of the recent information with the olaparib maintenance and with the NTRK inhibitors for the NTRK fusion transcripts.

Great. And then finally, Dr. Sohal, how do you envision that this guideline update will affect patients?

I think it expands our armamentarium for pancreas cancer patient management. It affords opportunities for better treatments, targeted therapies, which have hopefully higher efficacy and lower toxicity than standard chemotherapy, even though, as Dr. Laheru said, the proportion of patients being eligible for these therapies may be only around 5%. Still, in a disease where there are not many options, every 1 in 20 patients can get these therapies based on tumor genomic profiling and/or germline testing.

And the other slightly different but associated topic is that if germline testing finds something in the patient, a bad gene, then obviously, that patient's blood relatives can be tested for that germline finding, and there may be implications for further testing and surveillance of family members.

Well, thank you both for your work on this metastatic pancreatic cancer guideline update. And thanks for taking the time to speak with me today, Dr. Sohal and Dr. Laheru.

It's our pleasure, Brittany. Thank you very much.

Certainly. Thank you so much.

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