Choti Sheds Light on Research Developments in Pancreatic Cancer

Michael Choti, MD

Although the goal is to cure patients with pancreatic cancer through surgery, many patients who present with this disease are ineligible for resection at the time of diagnosis, making imaging and early detection imperative, said Michael A. Choti, MD.

Ideal surgical candidates are those with localized disease that is away from vital structures like veins and arteries, explained Choti, who is chief of Surgery at Banner MD Anderson Cancer Center. However, as more advanced imaging techniques enter the field, and more patients with borderline operability are recommended for surgery, multimodality therapy will have a larger role. Rather than receiving chemotherapy postoperatively, these patients can receive neoadjuvant chemotherapy.

Additionally, ongoing research is looking into ways to use molecular testing in order to personalize treatment for patients. While immunotherapy has had little impact in these patients thus far, a recent trial with pembrolizumab (Keytruda) may provide a breakthrough in this space.

The open-label, single arm, phase IIa trial (NCT02826486) is evaluating the safety and efficacy of the CXCR4 antagonist BL-8040, both as a single agent and in combination with pembrolizumab in patients with metastatic pancreatic adenocarcinoma. In the study, patients are receiving 5 days of monotherapy with BL-8040, followed by repeated 3-week cycles of pembrolizumab combined with BL-8040 every 3 weeks. Data for 29 evaluable patients presented at the 2018 ESMO Congress showed a median overall survival of 3.4 months in the entire population, and 7.5 months for those who received at least 1 previous line of treatment.

OncLive: What is the role of surgery in the pancreatic cancer paradigm? Has it shifted at all in recent years?

In an interview with OncLive, Choti highlighted ongoing developments in the field of pancreatic cancer.Choti: There are many changes happening in the treatment of patients with pancreatic cancer. The most common form, pancreatic adenocarcinoma, is still a very difficult disease and very life-threatening; few of these patients can be cured. As a surgical oncologist, the goal for most of us is to determine if we can cure the disease through surgery. Unfortunately, most patients who present with pancreatic adenocarcinoma are not operable at the time of diagnosis. These patients can either have metastatic disease or have locally advanced disease, precluding the ability to resect it.

Therefore, imaging is very important, and so is early diagnosis. If the tumor is resectable—that is, contained, no evidence of metastatic disease, and away from the vital structures—that patient is a candidate for surgical therapy. Of course, these are big operations depending on where the tumor is located: in the head of the pancreas, the tail, or the body.

What are the biggest advances being made in the field?

What is new in the landscape of patients with operable disease is the multimodality therapy. We are seeing more effective forms of systemic chemotherapy for patients with pancreatic cancer. We are aggressively bringing the regimens in that were being used for patients with advanced disease. Rather than giving chemotherapy postoperatively, we are seeing a strong trend toward neoadjuvant chemotherapy. This is mostly for patients with what we call borderline operability. More often than not, we are recommending systemic chemotherapy prior to surgery.We are learning more about the area of hereditary or familial high-risk pancreatic cancer. There is a lot of ongoing research trying to [find ways to] screen patients with high-risk disease. Clearly, early diagnosis and prevention are very important, but we are learning that there is a lot of room for improvement in our ability to detect pancreatic cancer.

We are learning more about certain mutations—for instance, BRCA mutation. These mutations are associated with breast and ovarian cancers, but we are learning that these also might have something to do with risk of pancreatic cancer. We are developing regimens to screen those patients, but there is still a challenge in how we are doing the screening. There is still room for additional research.

There is also the topic of how we can use molecular testing in order to identify or personalize the forms of therapy we use. Can we bring immunotherapy or targeted agents into pancreatic cancer? Unfortunately, most of the molecular information we are getting is not very [useful]. The standard treatments are still cytotoxic chemotherapies.

What is the role of immunotherapy in this space?

What should community oncologists be most cognizant of when treating patients with pancreatic cancer?

Additionally, there is a debate in the field on whether we should use radiation for patients with locally advanced disease. Pancreatic cancer that involves the arteries and veins is not initially operable, but perhaps there are other ways to manage these patients. For these patients, the standard, again, is chemotherapy.Right now, there are ongoing trials in immunotherapy for advanced pancreatic cancer. Currently, it appears that most pancreatic cancers are not immunogenic, so they are not good candidates for this type of treatment. In the current trials, we do not have any recommended effective immunotherapy agents, but there is potential for it in the very small population of patients with microsatellite instability-high tumors.Pancreatic cancer is a very aggressive disease that needs a multidisciplinary management if at all possible. Clearly, for patients that present with advanced metastatic disease, the role of radiation or surgical therapy are more limited. Usually, for those patients, a community oncologist may suggest newer regimens. Our goal is to not only to prolong survival but manage quality of life. What is important for community oncologists to understand in that sense is accurate staging.

If a patient's disease is resectable, they need to be managed in a high-volume center with an experienced team. There is curative potential. Sometimes, patients with borderline operable or even operable disease are not referred to receive surgery. We need to make sure that we are identifying the right patients.

Hidalgo M, Epelbaum R, Wolpin BM, et al. A phase 2a trial to assess the safety and efficacy of BL-8040 and pembrolizumab in patients with metastatic pancreatic adenocarcinoma (PDAC). Ann Oncol. 2018;29(8). doi: 10.1093/annonc/mdy288.006.