Sequencing Therapy in Patients With Resectable Pancreatic Cancer Under Investigation

Vincent Picozzi, MD

Vincent Picozzi, MD

Patients with pancreatic cancer typically undergo chemotherapy and/or chemoradiation followed by surgery with the intent to cure. However, this treatment landscape lacks data on sequencing chemotherapy in patients to optimize response. Treatment following surgery at this time remains unclear.

Patients with resectable pancreatic cancer from the Virginia Mason Pancreaticobiliary Cancer Database wereincludedin an analysis to determine the impact of neoadjuvant chemotherapy alone in this patient population. Data from this analysis were presented at the 2020 Gastrointestinal (GI 2020) Cancers Symposium by lead author, Vincent Picozzi, MD.

Picozzi said the goal is to identify patterns of recurrence which may demonstrate which patients are in need of subsequent therapy following surgery. Investigators can build upon these findings to make more intelligent decisions regarding appropriate therapy following surgery to maximize outcomes in patients with pancreatic cancer.

“The work is ongoing, and our goal is to come up with specific guidance in terms of who should actually receive chemotherapy and chemoradiation, and potentially what type of chemotherapy, following surgery to maximize their chance of cure,” Picozzi, director of the Pancreas Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, said.

In an interview withTargeted Oncology, Picozzi discussed the findings that were presented at the 2020 GI Cancers Symposium for patients with pancreatic cancer and how the results could impact the treatment of this patient population. He also highlighted observations from other pancreatic cancer clinical trials and the evolution of the GI cancer landscape as a whole.

TARGETED ONCOLOGY: Could you provide some background to the study?

Picozzi:The goal of treating localized pancreatic cancer is to cure it. To do so, we need to know how to optimally apply different forms of therapy, both chemotherapy and chemoradiation, in conjunction with surgery. In particular, when chemotherapy is used in neoadjuvant fashion, the best recommendation of treatment after surgery remains unclear. Usually, such patients have received both chemotherapy and chemoradiation prior to surgery, but in our institution, we typically use chemotherapy as a sole modality before surgery and make decisions about other therapy afterward.

TARGETED ONCOLOGY: What did you find in your study?

We looked at our data to see if we could begin to learn how a person’s response to chemotherapy and the pathological response of surgery might predict the likelihood of response. We had a group of 134 patients, and we analyzed the features of response at the time of surgery. Interestingly, we found that although the pathological response of the primary tumor to chemotherapy was prognostically significant when seen as a single variable, when seen in conjunction with other variables, such as the size of the tumor, degree of differentiation, and degree of null involvement, it actually ceased to have prognostic significance. We are trying to learn from the patterns of recurrence we have seen, which is about 30% local and 40% distant in total, which patients subsequent to surgery are in need of additional treatment. We can build upon this work so that we can make intelligent decisions regarding what to use after surgery to maximize a person’s chance for cure.

TARGETED ONCOLOGY: What would you like to highlight from these findings?

Picozzi:  The work is ongoing, and our goal is to come up with specific guidance in terms of who should actually receive chemotherapy and chemoradiation, and potentially what type of chemotherapy, following surgery to maximize their chance of cure. We will be presenting further for those interested to learn more about how we go about this.

TARGETED ONCOLOGY: What would be the next line of therapy after shrinking the tumor in the neoadjuvant setting in pancreatic cancer?

Picozzi:Let’s say we give a patient a course of chemotherapy and then they go to operation. We come up with some prediction as far as the likelihood of recurrence both locally in the region of recurrence and distantly elsewhere throughout the body. We can then say to the patient they have this percent chance for local recurrence. Chemoradiation would likely reduce the likelihood of recurrence by this amount, so we should consider this or not. In addition, you have this percentage likelihood of it recurring elsewhere in the body. Chemotherapy is thought to have this much impact on the risk of recurrence. We should proceed with additional chemotherapy or not. We are beginning to tailor a person’s post-surgical treatment to their particular situation and their own likelihood of response.

TARGETED ONCOLOGY: What are the other options available for this patient population?

Picozzi:Generally, these patients are treated according to a specific predesignated treatment protocol. The most common pathway would be for a person to get chemotherapy, chemoradiation, and then surgery. There is either very little or no chemotherapy given after that. There have been some studies that calls into question the role of chemoradiation preoperatively. The whole way that different therapies are integrated and sequenced is being reexamined at this time.

TARGETED ONCOLOGY: What therapies do you find particularly hopeful in clinical trials now?

Picozzi:There is promise in pancreatic cancer for a whole host of new types of drugs, such as drugs that impact the metabolism of cancer cells, new strategies for immunotherapy, drugs that impact the stroma, and other classes of drugs that offer new promise.

Another study that I am working within which I am very encouraged by is a study called the LAPIS trial. This looks at the impact of an anti-stromal drug called pamrevlumab (FG-3019) that inhibits a growth factor called connective tissue growth factor 1. It has been suggested from earlier studies that this drug added to standard chemotherapy, in this case, gemcitabine and abraxane, can either make the therapy more responsive to therapy in terms of frequency, magnitude, or the character of response. Early data are suggesting it might make patients more omittable surgery than would otherwise not. This is being tested in a randomized fashion as part of a registration trial to see if this drug in locally advanced pancreatic cancer can make an impact on tumor response and ultimately the ability to take a patient to curative intent.

TARGETED ONCOLOGY: As a whole, how do you see the treatment landscape of GI cancers shifting in the coming years?

Picozzi:Within the field of GI oncology as a whole, we are refining the role of molecular navigation in therapy, which is the importance of genetic analysis, in what situations it is used in and not. It really cuts across all areas of GI oncology. Another aspect that cuts across all areas of GI oncology is the role of effective immunotherapy and how that can be employed either on its own or in addition to chemotherapy. A third aspect of treatment is beginning to think of patients in subgroups. For example, in biliary cancer, as opposed to thinking of cholangiocarcinoma and gallbladder cancer as 1, it is best to think of it as 3 or 4 different diseases with different molecular profiles, different recurrence patterns, and ergo different treatment approaches.