Eileen O'Reilly, MD
As an immune-resistant disease, pancreas cancer has raised several challenges as investigators explore immunotherapy regimens to treat this patient population. While pancreas cancer has not demonstrated the same signal for immunotherapy as other diseases, several ongoing trials are investigating potential strategies that could help overcome this immune resistance, including combining immune agents together.
“That's what the current strategies in the clinic are all about. Can we reverse this inherent immune resistance, and can we make pancreas cancer an immune-responsive disease? I think people are optimistic – and I certainly am – that we will figure this out for pancreas cancer,” said Eileen M. O’Reilly, MD, associate director for Clinical Research, David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center.
During the World Congress on Gastrointestinal Cancers, O’Reilly spoke on the progress being made with immune therapies in pancreatic cancer, which she says is an area that is currently in flux. In an interview with OncLive
, O’Reilly discussed her presentation, as well as some of the treatment strategies currently being examined in the field.
OncLive: At the World GI meeting, you gave a presentation on whether progress is being made with immunotherapy in pancreatic cancer. Can you give an overview of that talk?
The topic for discussion here is what is happening with immunotherapy in pancreas cancer. I would say this is an area of flux. Pancreas cancer is traditionally considered to be an immune-resistant disease. It's characterized by the stroma, which is hostile. There's a lack of effector T cells, a lot of myeloid-derived suppressor cells, and really a dearth of the key immune effector cells and T-regulatory cells, so this may be part of the reason why we haven't seen the major signal in pancreas cancer with single-agent checkpoints compared to other diseases. However, there are a lot of strategies being pursued. A key question is if you can make pancreas cancer immune responsive. A strategy to do that is to combine immune agents together. We have some signal-seeking studies underway in the second-line setting to combine immune agents with chemotherapy.
For example, the Parker consortium is looking at combining gemcitabine/nab-paclitaxel and nivolumab (Opdivo) with CD40. There is pretty good preclinical data for that combination. Other examples of immune therapy and chemotherapy are a phase III trial that is about to mature looking at FOLFOX and pegylated interleukin-10, again, altering the immune microenvironment. This study will complete recruitment probably late this year or early next year. Hopefully, we will have data next year.
Another area of interest is CSF1R targeting. Some data were presented at the SITC meeting last year for a cohort of patients with advanced heavily pretreated pancreatic cancer who had received a CSF1R inhibitor and nivolumab. There were a notable number of responses and durable responses in 5 patients. This is resulting in that combination being developed further with chemotherapy in the second-line setting in pancreas cancer. I think there is more to come on that topic.
Another point to keep in mind is that there is a subset of patients with mismatch repair deficiency in pancreas cancer. It's small, probably about 1%. For that group of patients, immunotherapy with single-agent checkpoints may have a role. We are still learning where strategies with adoptive T-cells have a role in pancreas cancer. I would say it's an exciting time, but we still have to prove that there is a signal for immune therapy for the average patient with this disease. There is more to come.
What are some agents showing promise right now in early phase studies?
Agents that are being evaluated in early phase settings in pancreas cancer, such as PEGPH20, include modulation of the stroma. That agent is in frontline testing in a randomized phase III study in a biomarker-selected population of patients with elevated levels of hyaluronan. Patients receive either gemcitabine/nab-paclitaxel plus PEGPH20 or gemcitabine/nab-paclitaxel alone. That is based on phase I and II data, suggesting that the approach may have value in that setting. We have to temper that a little bit with some data in a different setting in metastatic disease, and using a different cytotoxic combination where there wasn't an obvious signal. In fact, the signal may have been detrimental. There's more to be elucidated from that trial. I think we are looking forward to seeing the maturation of the phase III.