Treatment Modalities Evolving in Pancreatic Cancer

Mark J. Truty, MD

Pancreatic cancer is poised to be one of the leading causes of cancer-related death over the next 10 years, according to Mark J. Truty, MD. Though difficult to treat, there has been recent progress in the treatment of patients with this disease, he adds.

Neoadjuvant therapy approaches are currently being explored in clinical trials. For example, an open-label phase III study is exploring sequential neoadjuvant chemoradiotherapy followed by curative surgery compared with primary surgery alone for patients with resectable, nonmetastasized pancreatic adenocarcinoma (NCT01900327). The primary endpoint of the study is 3-year survival rate.

OncLive: Please give an overview of your talk.

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Gastrointestinal Cancers, Truty, an assistant professor of surgery at Mayo Clinic, discussed sequencing treatments and advances in imaging technology in pancreatic cancer.Truty: I spoke about the management of what we call nonmetastatic pancreas cancer. Pancreas cancer is a very deadly disease, and, as most people are aware, it is very stigmatic. The reason it is so deadly is that the majority of patients already present with metastases. Even when it is displayed on scans, most patients probably have micrometastatic disease. Therefore, I discussed the surgical management of these patients.

What is being done currently to address these issues?

Could you provide more detail on sequencing in this disease?

Specifically, there are 2 main issues that we have had over the past 3 decades. One is that many patients are going to the operating room for surgical resection of their tumor when they probably shouldn't. The second issue is that many patients are probably being denied an operation when they should get one. The challenge is trying to decipher how to sequence everything that we currently have to get the best outcome.There are 3 main treatment modalities for pancreas cancer: surgery, chemotherapy, and radiation. People have always thought of these as independent things, but we are finding out that patients who achieve the best outcomes are receiving all 3 modalities. It is like baking. You can't just take all of the ingredients and put them in a bowl. You must take those ingredients—the modalities—and put them in the right sequence with the right amount to get the product that we are looking for. The product that we are looking for is survival.Things have changed dramatically since 2011 when level 1 data proved that modern combinatorial chemotherapy was markedly effective in pancreas cancer. Now, we are using that data that were initially done in the metastatic setting and applying it to patients who have seemingly resectable or what we call locally advanced disease. We are finding significant rates of efficacy in those patients with associated survival.

Are there any ongoing surgical-related clinical trials in this space?

The new thing is neoadjuvant therapy where we will give them all therapy upfront. The question is how to do that. What sequence? How many cycles? How do we know if we are doing it appropriately to get the best outcome? That is what we have been working on to optimize that approach.The most exciting trial is a study on metabolic imaging. Right now, what happens is that patients have pancreas cancer and we subject them to chemotherapy prior to the operation. The key thing is that, if you are going to give chemotherapy prior to surgery, you must prove that the chemotherapy is working. Modern imaging, such as CT scans, do not tell you whether the tumor is alive or dead.

Where do you see the future of this treatment landscape going?

What should community oncologists take away from your presentation?

So, we are focusing on and relying more on metabolic imaging, PET imaging, and these more advanced PET images, such as a PET/MRI. There is now a multi-institutional prospective trial looking at metabolic imaging to determine if the chemotherapy these patients are getting is effective. If it’s not, then we will switch them to an alternative therapy before making the decision to go to the operating room.It is exciting; all of these changes have been dramatic in the last 5 or 6 years. We never had any drugs that were effective other than single-agent gemcitabine. Now, we have 2 combinatorial regimens and there are more phase III studies coming out. Just like metastatic colorectal cancer, which was formally a very fatal disease that now has so many treatment regimens, we are hoping the same thing will apply with pancreas cancer.The key thing is to never settle for the first opinion. It is such a stigmatic disease; people find out that they have pancreas cancer and think, “There are no options.” Things have changed dramatically and we have a lot more options for patients who would have otherwise been considered to go to hospice; we are now seeing a significant survival benefit.