Next-Generation Sequencing for All Patients With Pancreatic Ductal Adenocarcinoma

At the 2023 World Congress on Gastrointestinal Cancers, Philip Philip, MD, Wayne University, defended the position of doing next-generation sequencing for all patients with pancreatic ductal adenocarcinoma.

In this debate, Dr Philip highlighted the benefits to NGS, such as identifying drugs outside the standard of care that may be successful, and allowing a patient to be enrolled on a clinical trial. Dr Philip concluded, "To help the patients, to move the field forward, to help the research, to get more new drugs into the patients with pancreatic cancer, to extend their survival, NGS will be important."

Transcript:

Hi, I am Dr. Philip Philip. I'm a professor of oncology at Wayne State University and Henry Ford Hospital in Detroit, and I specialize in gastrointestinal and neuroendocrine medical oncology. I'm here today in the 2023 World Congress on Gastrointestinal Cancers. This is the 25th anniversary of the meeting, and I'm really very glad to be here. I took part in a debate regarding the use of next-generation sequencing, or NGS, in patients diagnosed with pancreatic cancer. The debate was about whether we should be using NGS in all patients or not. I personally use it in all my patients. For that reason, it was a bit of an easy debate to support that kind of thinking or strategy.

The major reason is that we need, really, better treatments and more treatments in patients with pancreatic cancer. The next-generation sequencing serves 2 purposes. One is it helps to get the patients on drugs that they can't get it if they follow the standard of care. And the second thing is that it helps patients to go on clinical trials. Because as we all know, there are a number of new drugs coming along, and the next-generation sequencing will allow us to put patients on clinical trials because of the matching between a molecular abnormality and also the trial.

Just to give an example of how we're extending the use of NGS to get more patients on treatments that otherwise we wouldn't have done that, and an example I have is 2 weeks ago, I had a patient who failed treatment on gemcitabine and nab-paclitaxel. The guy is 72 years of age, had some difficulties with chemotherapy, but this patient had a KRAS wild-type tumor. And in those patients, we know that there is an increased frequency of targetable mutations. This patient had an FGFR fusion, and I started the patient on treatment with an FGFR-targeting treatment. Just an example.

If I hadn't done NGS, I would have never been able to really use a drug like an anti-FGFR in this patient, which really leads me to the real issue about NGS. What is really going to help me today? Ten-percent of the patients have wild-type KRAS unmutated tumors. Those patients I mentioned to you earlier, they have a preponderance of targetable mutations. But even without the RAS wild-type, we also have now drugs that are targeting KRAS itself. And as you know, there are KRAS mutations, D, 12D, 12V, 12R, and these are targeted by different drugs. Knowing which one helps to send your patient to a clinical trial.

We know about the BRCA mutations, for example, and possibly other DNA repair mutations that can be seen in those patients, and they can also benefit from some standard treatments like platinum, PARP inhibitors, but also to be in clinical trials which take patients who have DNA mutation defects. Not to mention, patients who have MSI-high can go on immunotherapy, tumor mutation burden high, they go on immunotherapy. So collectively, we are helping the patients by doing next-generation sequencing because we can give them better treatments or put them on treatments that are FDA approved but not yet for pancreatic cancer because they have a mutation, like the example I gave you of the FGFR. But also, it helps us to put patients on clinical trials.

This is the only way we're going to really improve the outcome of this disease. The standard chemotherapy we use isn't really that helpful. The median survival remains at 12 months and we need to make better. And doing the NGS is really the first step in really going into the strategy of personalized treatments for patients based on molecular makeup. The patients want it. They want us to do it because if we don't look for these mutations... Some will call them rare mutations. I don't disagree. They're not common. But again, if you don't look for it, you're not going to find it. And if you don't look for it, you don't find it, then the patient may be denied a treatment that can help to extend their life.

This is really in a nutshell what I feel:  NGS is very helpful in this disease. And again, there are challenges, no question. The solution is not to not do NGS but try to go over and try to find solutions to these challenges. For example, the amount of tissue we get from biopsy material, sometimes it's not enough to do NGS. There are solutions around it. One of them would be to repeat the biopsy. The other one would be to do liquid biopsy. There are ways around it. And certainly, there is the cost of the NGS, which is fortunately going down with these procedures or assays being done in a larger scale. And we're seeing a drop in the cost of these tests.

Certainly, the patients are well-served by having them. The patients are increasingly aware of them and the patients are always asking me about, at least in my practice, why I don't have a molecular profiling done on my patients. As it happens, whenever I see a new patient with pancreatic cancer, I do molecular profiling, NGS being part of it. So for me, NGS is part of the initial workup of the patient, and I believe that it should be considered as an initial workup of patients as we go forward.

Remember, it's the first step in us moving into a more personalized treatment for patients with advanced pancreatic cancer. And in fact, even in patients who have localized pancreatic cancer, resectable, there is now opportunities. Like, in the United States, we have a clinical trial that really looks into the addition of olaparib in the adjuvant maintenance setting in patients who have resected pancreatic cancer, and I think more of this kind of work is going to be happening.

To help the patients, to move the field forward, to help the research, to get more new drugs into the patients with pancreatic cancer, to extend their survival, NGS will be important. But I agree, it's not going to be the only thing. We have to build on the NGS. But at least we have a way to start the personalized treatment.

Source:

Philip P. Molecular Therapies in Pancreatic Ductal Adenocarcinoma: NGS for All or None – PRO. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.