MM-398 and Other Novel Agents Improve Outlook in Pancreatic Cancer

Philip Philip, MD, PhD

Since the majority of patients with pancreatic cancer present with metastatic disease, treatment options are often limited. Novel therapies and combinations are critical to improving the outlook for patients, said Philip Philip, MD, PhD, professor of Oncology at Karmanos Cancer Center, Wayne State University School of Medicine.

Fortunately, promising investigational agents are beginning to emerge, including MM-398, a nanoliposomal encapsulation of irinotecan. The FDA recently granted the drug a priority review based on the NAPOLI-1 trial. In the study, adding MM-398 to 5-FU and leucovorin significantly improved survival and response rates compared with the two drugs alone in patients with gemcitabine-refractory metastatic pancreatic cancer. A final approval decision is scheduled to be made by October 24, 2015.

In an interview with OncLive, Philip discusses how MM-398, the GVAX vaccine, and other novel treatments and approaches are offering new hope to patients with pancreatic cancer.

OncLive: What is on the horizon for the treatment of pancreatic cancer?

Dr Philip: This is an exciting time for patients with pancreatic cancer because we have reached a point in time where we know more about the biology of the disease and we know more about the genetic changes and mutations in this disease than ever before. Most importantly, there is much more public awareness of pancreatic cancer, funding has increased, and there has been an increase in the number of investigators that have focused their careers on pancreatic cancer.

As a result, the range of drugs that are available to us is really very wide now. There are many drugs available to patients based on their genetic abnormalities. We now have drugs against signaling pathways and drugs that target the components of the stroma of the tumor cells. Immunotherapy is also just beginning in this disease. There have been major advancements in other cancer types over the last year or two. Many of them look very promising and are really changing how we look at this disease.

What considerations need to be made when deciding which treatments to offer which patients?

When a patient comes to you for the first time with a diagnosis of pancreatic cancer, we want to give them the best treatment we can offer. Right now, that is combination chemotherapies. We have two major treatments; one is gemcitabine plus nab-paclitaxel and the other is the FOLFIRINOX treatment. Some patients qualify for both treatments, and some patients are not able to tolerate either, especially patients who have liver dysfunction or who are over 75.

How is immunotherapy evolving in pancreatic cancer?

We have started seeing some of the benefits of immunotherapy. There was a pilot study that tested the GVAX vaccine and CRS-207 compared to chemotherapy or CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma. That study showed that there was some benefit to treating patients with the GVAX vaccine that have been previously treated with chemotherapy and failed. The next step will be to confirm if this is really an effective approach; there is a phase III trial ongoing. There are also studies looking at the PD-1 inhibitors that have just started. We are still in very early days with that.

What is the role for the novel agent MM-398 in pancreatic cancer?

MM-398 is liposomal formulation of irinotecan, which we have been using to treat pancreatic cancer as part of the FOLFIRINOX regimen. It has been used in a number of other malignancies, such as colon cancer and gastric cancer. The liposomal formulation of the drug makes it more favorable. It really improves its distribution into the tumor tissue and also prolongs its half-life in the blood, and as a result, patients will potentially have a better benefit and more tolerable toxicity.

MM-398 has gone through a phase III trial in which it was administered with or without 5-fluorouracil and leucovorin. The study showed that the triple combination was superior in terms of the progression-free survival and the overall survival. Hopefully, that will lead to an application to the FDA, which will be successful, and as a result the combination will be another option available for our patients, at this time in the second-line setting.

What kind of impact would an approval of MM-398 have?

It is going to be an incremental impact; it is not going to be a cure. In terms of the life expectancy for these patients it will not add years to their life but it will have a clinically meaningful impact that will prolong their survival. Not every patient will be able to get it, but for those who are eligible, there is potential. Any additional months of survival are significant in this patient population.