Emerging Approaches: Pancreatic Cancer Systemic Therapy - Episode 15

Pancreatic Cancer: Unmet Needs and Future Directions

February 20, 2019

Transcript: Shantal Ginsberg, RN: Can you talk about ongoing, unmet needs that you feel you have in treating metastatic pancreatic cancer?

Paul E. Oberstein, MD: Yes. I think the most important point is that we are not doing well enough. Our patients are not living as long as we would like them to live. Although there has been progress in the last few decades in treating pancreatic cancer and there are new agents available, there still is only a limited benefit from any of these agents for the average patient. And so we really have to continue focusing on the bottom line, which is improving survival, improving duration of survival, and along the way, continuing to give patients good quality of life.

I think specifically there’s a need for new agents, but even before we get to new agents that we can use, we have to understand how to use the agents we have for the maximal number of patients. And disturbingly, many, many surveys show that a lot of patients with advanced pancreatic cancer don’t receive any therapy or don’t receive optimal aggressive therapy, either in the first-line or in the second-line setting. And part of that is because there’s historically been a fear of treating these patients. They’re very sick, and the agents were not as effective as they are today. And some of it is that clinical trials pick very select patients, and they don’t always tell us how to treat patients who don’t fit those clinical trials, who are not as strong, as healthy, or as functional as the patients who are in the clinical trial.

We definitely need to continue treating those patients. They have pancreatic cancer. Many of them in our clinics and in our practice will benefit from aggressive and ongoing chemotherapy in the first and second line, and we need to keep telling others about how those patients did, so that we can report on them and understand where to use agents and how to modify things for elder patients, for patients with a lot of symptoms, and for those who may have liver dysfunction who still should have options for therapy.

In addition, there are a lot of questions about how to sequence chemotherapy, how long to give chemotherapy, when to give maintenance chemotherapy, when to begin second-line chemotherapy, and whether or not one agent is better than the other in first-line chemotherapy. These are all questions that are being addressed in some way or another in clinical trials, and we eagerly await those results, which will hopefully clarify for us the best way to treat patients going forward.

Perhaps more importantly than learning about sequencing is the incorporation of new agents in therapy. And there are several exciting clinical trials that are being conducted in patients with advanced pancreatic cancer. Unfortunately, there have been many trials that were exciting and didn’t yield positive results, so we have to temper that enthusiasm until we have final results of these clinical trials. But there are agents, especially agents in the third-line setting, including agents that target something called the stroma. So they try to target the area around the pancreatic tumor that’s made up of not pancreatic cancer cells themselves, but the supporting cells that support the tumor, often prevent chemotherapy from being delivered to the tumor. And there are several clinical trials, including a phase III clinical trial, looking at strategies to break down that stroma and hopefully increase the delivery of chemotherapy for patients with pancreatic cancer.

The next group of clinical trials that are very exciting are things that are focused on patients with specific genetic mutations. So we know that somewhere between 5% to 10% of pancreatic cancer patients will have a mutation in a gene in their tumor that contributes to DNA repair, to fixing mutations. We think that those patients are both more sensitive to chemotherapy and maybe more sensitive to specific chemotherapies, including a medication called a PARP inhibitor. And there are several of them that are undergoing clinical trials currently in advanced pancreatic cancer patients. We eagerly await results of those clinical trials and other ongoing clinical trials that may increase options for patients.

Another option is immunotherapy. So immunotherapy has been wildly successful in a select number of cancers. Unfortunately, to date, it has not helped pancreatic cancer patients except for the small group of patients who have something called microsatellite instability. We’ve seen several of those patients. We’ve treated them with immunotherapy with excellent results, and so we emphasize in our clinic the importance to test every patient for microsatellite instability.

But the real goal of ongoing research is to try to identify how we can get those agents, these immunotherapy agents, to benefit a larger number of patients, not just the 1% to 2% who are microsatellite unstable. And the strategies to do that include adding secondary immunotherapy, combining it with chemotherapy, or perhaps adding radiation therapy into the immunotherapy, which has shown success in a small number of patients. These are all agents that are being tested in clinical trials and are, I think, exciting things. We are both doing clinical trials and eagerly awaiting the results of those clinical trials.

Finally, we think that there are going to be many agents that help a small group of patients. And the only way to get those patients into the trials is to properly and comprehensively characterize every patient with pancreatic cancer, including looking at the patient, their characteristics, and their tumor. And so we are looking more broadly, and some groups are trying to look at every patient to sequence their tumor to understand which genes are mutated in the tumor, and then use that information to go into the lab and back into the patient to understand which specific chemotherapy, immunotherapy, or experimental agents will benefit a patient with specific mutations in their tumor.

And we’re very excited about results in the lab, especially in mice with pancreatic cancer in which we can give them specific mutations and show how to treat those mutations. We really need to get the next step and translate that into patients. And that’s going to happen through large collaborations between many cancer centers and many treating physicians incorporating their patients in clinical trials, reporting those results, and sharing that information with the community, so that more treatment options become available for patients with pancreatic cancer. I would say that we are lucky that we have new options to treat these patients. There’s clearly a tremendous amount that still needs to be done. We shouldn’t avoid the options we have, but we have to learn how to make them better. And I think ongoing clinical trials and research are going to help us achieve that goal.

Shantal, I’d like to thank you for participating with me today in this OncLive Insights® presentation about treating pancreatic cancer. I hope that this was educational. Thank you very much for your insights that you added and thank you everyone for participating.

Transcript Edited for Clarity