Novel Treatments Emerging in Pancreatic Cancer

Carlos Becerra, MD

Although response rates were low, patients with metastatic pancreatic cancer experienced a significant decrease in tumor burden after being treated with chimeric antigen receptor (CAR) T cells, according to Carlos Becerra, MD.

In an effort to expand the data on CAR T-cell therapy in pancreatic cancer, there is an ongoing phase I study investigating CAR T-cell therapy in patients with unresectable pancreatic cancer (NCT02744287). This study is designed to determine the safety of the administration of anti—prostate stem cell antigen CAR T cells. Additionally, it aims to evaluate the safety of rimiducid infusion after CAR T-cell therapy is administered, as well as the persistence of the CAR T cells over time after a single rimiducid infusion. This study is currently enrolling patients and is estimated to be completed in 2020.

Additional approaches, including checkpoint inhibitors and novel chemotherapy regimens, are also being explored in this landscape.

OncLive: Can you provide an overview of your presentation on the management of pancreas cancer?

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Gastrointestinnal Cancers, Becerra, the interim chief of Oncology for Baylor Scott & White Health — North Texas, and medical director of the Swim Across America Innovative Clinical Trials Center at the Charles A. Sammons Cancer Center at Baylor University Medical Center at Dallas, discussed the current management and emerging therapies for patients with pancreatic cancer.Becerra: Pancreas cancer is one of the leading causes of death related to cancer. We do not have good treatments. We have made some progress in pancreas cancer, particularly with metastatic disease, since many patients present to an oncologist already with metastatic disease.

We have made some progress over the past 7 or 8 years with the new chemotherapeutic agents. We have been investigating the sequencing of the agents to improve overall survival. It is not uncommon today to see patients 15 to 20 months after they have been diagnosed who are alive and doing well. That speaks to the fact that the newer agents are doing the work. However, we need to go beyond that.

Is there a role for checkpoint inhibitors in this field?

The new era of targeted therapy and immunotherapy is going to provide the additional benefits that we need for our patients with metastatic pancreas cancer.The immune checkpoint inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) are being studied in pancreas adenocarcinoma. We think that there is a subgroup of patients who might benefit the most. These are the patients whose tumors are microsatellite instability-high (MSI-H). We are currently studying those patients as they become our target population.

Are there any ongoing trials that are showing promise?

[Pembrolizumab] has been approved across the board for all MSI-H tumors. [There is a subgroup of patients with] MSI-H tumors who have metastatic pancreas cancer.There are several trials that we are excited about. As we break down the molecular makeup in mutations that occur in pancreas cancer, there is a subgroup of patients who have mutations that we think might be targetable.

What data have been shown with CAR T cells?

In addition to that, we are heavily studying immunotherapy in these patients. We are looking to discover if there will be immune checkpoint inhibitors in combination or CAR T cells that have been modified to recognize a specific target in the tumor to attack.There are very little data available. There is a study conducted from the investigators at the University of Pennsylvania investigating CAR T cells directed against mesothelin. It was presented by Dr Gregory L. Beatty at the 2017 ASCO Annual Meeting. It showed some interesting results. Although the response rate was low, there were responses in patients with metastatic disease whose tumor burden decreased significantly after being treated with CAR T cells.

Where do you envision the treatment landscape heading in the next 5 years?

We are currently conducting a study at Baylor Scott & White Research Institute with CAR T cells directed against a different target. This study has a spin to it which is using an activating agent called rimiducid for patients with metastatic pancreas cancer who have progressed on first-line chemotherapy. I see that chemotherapy is here to stay. We already have several backbones of chemotherapy that we can use. In addition to that, targeted therapies are making their way into a subpopulation of patients whose tumors have certain mutations.

Is there anything else that you would like to add?

In addition to that, we are exploring and expanding immunotherapy to attempt to improve the outcomes. In the next 5 years, there will be combinations of different regimens to improve the overall outcomes of our patients.We spoke about neoadjuvant chemotherapy and its potential role in that subpopulation of patients who have marginally resectable pancreas cancer. The potential role of radiation therapy is a way to control the disease locally in order for the tumor to become resectable or have the initial landmark to be margin negative. That is what we call R0 resections, which is an important initial step.