Multidisciplinary Collaboration Plays Key Role in Pancreatic Cancer

Kian-Huat Lim, MD, PhD

Discussing the importance of multidisciplinary collaboration in the treatment of patients with pancreatic cancer, Kian-Huat Lim, MD, PhD, explained that for those with localized or borderline resectable disease, early engagement between surgeons, radiation oncologists, and medical oncologists facilitates more effective treatment planning.

“We need to provide as many support [options] as possible for the patients and their families,” Lim said in an interview with OncLive^®.

In the interview, Lim expanded on the role of multidisciplinary collaboration in the treatment of pancreatic cancer and highlighted the need to enroll patients in clinical trials, even after initial diagnosis. In a previous article, Lim expanded on factors to consider when selecting chemotherapy regimens for patients with locally advanced or metastatic pancreatic cancer.

Lim is a medical oncologist and an associate professor of medicine in the Division of Medical Oncology at the Washington University School of Medicine in St. Louis, Missouri.

OncLive: What is the importance of multidisciplinary collaboration when diagnosing and treating patients with pancreatic cancer?

Lim: [Multidisciplinary collaboration] is important for various reasons. In overall treatment planning for patients who have localized disease or borderline resectable, locally advanced disease, we need to get the surgeons and the radiation oncologist involved, because these are all the modalities we think about when we are trying to formulate a plan for any patient at the beginning [of treatment].

For example, for patients who have early-stage, localized disease that is borderline resectable, you want to have established collaboration and communication with the surgeons from the get-go. If you tell the surgeons that you're going to give [neoadjuvant] chemotherapy, you have the surgeons evaluate the radiographic imaging before, during, and after several months of chemotherapy, when the patient will become a surgical candidate. We also have to be mindful that along the way of chemotherapy, patients need to maintain a certain level of physical activity and physical robustness in order to go through surgery.

For patients whose [tumor is] not resectable, after several months of chemotherapy, you need radiation oncologists to come in and provide some input on whether radiation would help control the localized disease. We have to be mindful that we are giving rather toxic chemotherapy to these patients, and very few of them can tolerate this chemotherapy for months [on end]. Eventually, we come to a point where the patient needs to have a chemotherapy break, or the body is tired out. In that case, radiation can be a modality to consider in controlling local disease. If the patient is not resectable, this will provide a break from chemotherapy.

Are there any other specialists you routinely consult to assist in the treatment of patients with pancreatic cancer?

Another important group of physicians that we work with are gastroenterologists. In patients who have disease in their head or body of the pancreas, more likely than not, they're going to have obstructive jaundice as well. We need the help [of gastroenterologists] putting a stent to maintain patency of the bile ducts while we are treating the patients.

[Pancreatic cancer] is a disease associated with a lot of other issues, including diabetes. Diabetes is frequently a hallmark of cancer afterward, so you need an endocrinologist to be involved. [Patients could] have nutritional problems because of pancreatic insufficiency. Pain is an issue for a lot of patients. You need to have pain specialists involved as well in solving very severe cases.

And lastly, [we involve phycologists] for patients and their families. At Siteman Cancer Center and many major cancer centers, psychologists or palliative care specialists are on board, as well. This is a disease that is very complicated and is unfortunately associated with a poor prognosis, and treatments are associated with significant adverse effects.

What is the importance of enrolling patients with pancreatic cancer to clinical trials? Is there a disease setting in which clinical trial enrollment is most paramount?

If you look at the 5-year survival rates for all cancer types, [pancreatic] cancer still has a worse prognosis. We need newer therapies, and the only way to achieve that is by enrolling patients [in] clinical trials. Three [common] regimens [used for the treatment of pancreatic cancer—FOLFIRINOX, NALIRINOX, and gemcitabine plus nab-paclitaxel [Abraxane]—all came from clinical trials. They were found to be better than an older regimen, and we then adopted them to the current standard of care. That's how we evolve and move forward.

There are a lot of newer therapies being tested. There are new drugs coming out, and this is a disease that is not very common. You see [approximately] 60,000 cases per year in the United States, but not many patients are robust enough to go to clinical trials when they were diagnosed. Therefore, on top of [the limited number of cases], you're basically looking at maybe 20% to 30% of patients who are eligible for clinical trials from the get-go.

If a patient is robust enough [for a clinical trial], it makes sense [to consider enrolling them], based on the severity of the disease, the poor outcomes, and the limitations of the treatments that we with standard regimens. None of them are curative. It makes sense for patients to consider clinical trials. This recommendation is also in the National Comprehensive Cancer Network Guidelines, as well. Clinical trials should be strongly considered, if available, regardless of [the stage of the disease].

Is there any ongoing research in pancreatic cancer that you or your colleagues are involved in that you would like to highlight?

We have a few clinical trials ongoing at Washington University. We're fortunate enough to be awarded a [Merit Extension Award] from the National Cancer Institute [(NCI) in 2023 to provide support for cancer research, training, prevention, and community outreach programs].

One clinical trial I want to highlight is a [the phase 1/2 RAMP205 trial (NCT05669482)] first-line metastatic pancreatic cancer trial that includes gemcitabine plus nab-paclitaxel, a MEK inhibitor [avutometinib (VS-6766)], and a FAK inhibitor [defactinib]. This is based on preclinical studies done here by David G. DeNardo, PhD, at Washington University. He was the main leader, but he collaborated with many other outstanding researchers from the University of Pennsylvania, Dana-Farber Cancer Institute, the University of Michigan, and more. They found that this regimen is quite promising, at least in mouse models, and we have this study open for patients with newly diagnosed and pretreated metastatic pancreatic cancer. We have enrolled quite a few patients nationwide, and we found that there are some promising observations in terms of response rate, but we need more patients to [add to these data].

We also have [a phase 1] trial [NCT05685602] in the second-line setting where we combine gemcitabine and nab-paclitaxel with the IRAK4 inhibitor CA-4948 [emavusertib]. This came from research in my lab and is running through the NCI, and it is open in multiple institutions.

And I also want to highlight [a phase 1 trial (NCT05111353)] we have at Washington University, in which we use a customized vaccine. Pancreatic cancer is known to have low immunogenicity, meaning it does not respond to immunotherapy as you see in other cancer types. There are a lot of studies that show that the immune system does not mount a response [to pancreatic cancer]. The immune system can't see cannot see [the cancer cells], mainly because there are not a whole lot of mutations in pancreatic cancer cells. What we can do is try to take a piece of these tumor cells and do some complicated computational analysis and predict what would be a good antigen or protein expressed in these tumor cells to use to educate [a patient’s] immune system in the form of a vaccine.

We take a piece of tumor, then generate a vaccine out of it, and you give the vaccine back to the patient. Data from our institution shows that this is a very promising approach. Some patients are able to achieve long-term benefit. I believe that is the future for any cancer treatment. The immune system—if you're able to engage it and it works—will give you a durable response and long-term disease control without the systemic AEs from chemotherapy.

We strongly encourage that, even if [a patient] has a new diagnosis of pancreatic cancer, if you are able to and patients are willing to, refer them to an institution for clinical trials. These are patients we would like to talk to and introduce them to options. A lot of time, when we see patients in our institutions, they have been heavily pretreated, and a lot of them are not in the best shape when they're being considered for clinical trials, and that is something that we're struggling with. It would be nice to be able to see them at [at the initial diagnosis].