Surgery Remains the Gold Standard in Pancreatic Cancer Treatment

Partners | <b>Cancer Treatment Centers of America</b>

In an interview with Targeted Oncology, Katherine Poruk, MD, surgical oncologist, Cancer Treatment Centers of America, discussed the pancreatic treatment paradigm with an emphasis on the role of surgery.

Treatment of pancreatic adenocarcinoma is largely dependent on oncologic surgery, according to Katherine Poruk, MD. This is because the systemic therapy landscape for this disease is just starting to expand beyond chemotherapy.

Surgical procedures exist and are effective for patients with resectable and borderline resectable pancreatic tumors. The clinical issue is introduced when patients have metastatic disease because surgery becomes more difficult and often chemotherapy or radiation therapy is needed. Modern advances in care have also brought targeted therapies into the landscape, but there remains in gap in efficacy compared with other gastrointestinal cancers.

In an interview with Targeted Oncology™, Katherine Poruk, MD, surgical oncologist, Cancer Treatment Centers of America, discussed the pancreatic treatment paradigm with an emphasis on the role of surgery.

TARGETED ONCOLOGY™: Can you discuss the options that are currently available to treat patients with pancreatic cancer?

Poruk: Pancreatic cancer is unfortunately one of the more deadly cancers we treat. The 5-year survival currently is about 8% to 9%, and a lot of this is because most patients will present with either unresectable tumors, or they have metastatic disease. So, at the current time, the best option for therapy is surgery, and in about 20% to 25% of people, surgery is the mainstay of their treatment.

We remove these tumors either with a pancreaticoduodenectomy, which is a Whipple operation, during which removes the head of the pancreas, part of the duodenum, the stomach, and the gallbladder, and that reconstructs everything back in the normal atomic position. If there's a tumor in the tail of the pancreas, the patient undergoes what we call a distal pancreatectomy, in which case the spleen is also removed. In patients where this surgery is able to be done, there's usually around a 20% 5-year survival.

A lot of times when a patient is a surgical candidate, we will also give them chemotherapy, and sometimes radiation therapy. They'll either receive chemotherapy prior to surgery, which is called neoadjuvant, chemotherapy or after surgery called adjuvant therapy. And the timing of this often depends on the size of the tumor, and whether or not we think the tumor can be safely resected.

The other thing to mention is s with comorbidities. How healthy patients are is usually decided in conjunction with conversations with their medical oncologist. And the other patients where their tumor is either determined not to be resectable because the tumor is invading other organs or encasing necessary blood vessels, chemotherapy is the mainstay of treatment.

Whether the tumor is resectable or not, the 2 main chemotherapies we give are gemcitabine or the FOLFIRINOX regimen. Gemcitabine was sort of the main treatment for the longest time and FOLFIRINOX is newer, it was shown in trials in 2010 to almost double survival in people with metastatic cancer. So, for that reason, it's also become a very viable option in patients. The decision as to which chemotherapy is best is made in discussion with the medical oncologist and oftentimes it's due to the side effect profiles of both FOLFIRINOX, which is a little bit more toxic to some patients. So, patients need to be not healthier, but a little bit more robust to be able to tolerate it. So, it becomes a conversation with their medical oncologist.

Based on clinical trials, what treatment strategies are showing promise right now?

A lot of the trials that are happening right now are often due to timing of chemotherapy. Some of the bigger trials in surgical oncology are really trying to determine whether we should be giving everybody chemotherapy upfront prior to surgery, or if people can have surgery first and then have adjuvant therapies. That's sort of the most promising and the most interesting that's coming down in the surgical oncology pool right now.

Can you discuss novel biomarkers in pancreatic cancer?

Unfortunately, compared to other cancers, like prostate, for example, we don't have a good biomarker or a good screening marker in pancreatic cancer. We do have CA19-9, but that's not very good as a screening marker. It tends to be used for prognostication. So, we'll measure the levels when you're diagnosed, and we follow those levels over time to see how you're responding to therapies. So, there's not a lot of good markers in the blood.

We do recommend that all patients undergo genetic testing of their tumors. So, we'll do a genomic profile, we have found that some of the more common mutations are at KRAS, and also in SMAD4, tp53, and CDKN2A. We're also doing more work on how we can better prognosticate patients to help determine what therapies might be best for them.

How are targeted therapies being explored in pancreatic cancer currently? Is there any invocation into optimal timing of surgery and targeted therapies?

There have been some small studies with targeted therapies. Unfortunately, we haven't found as much promise with targeted therapies in pancreatic cancer as there are with some of the other cancer. And most of the work in targeted therapies are in the metastatic cancer setting. For example, there's olaparib [Lynparza], which is used in patients with BRCA1 and BRCA2 mutations. These are mutations that most people would most likely associate with breast cancer, but BRCA2 especially has been shown to have a higher propensity for prostate or for pancreatic cancer. And in patients with metastatic pancreatic cancer who have a BRCA1 or BRCA2 mutation, and have been on a platinum-based therapy, their medical oncologist may elect to put them on a targeted therapies such as olaparib as a maintenance therapy. There's also been some work with pembrolizumab, which is an anti-PD-1 antibody, and there has been some demonstration that these could be useful in patients who have MSI-high tumors. But similarly, these are used in patients with metastatic pancreatic cancer, who have been on other therapies like FOLFIRINOX or gemcitabine and progressed or have not had a good response.

So, some of the main targeted therapies at this time are used primarily in the metastatic setting. At the time, it's not really anything that we're utilizing for surgery.

Considering some of the unmet needs in the field, what surgical advances do you see being moved forward for these patients?

The most important thing when it comes to pancreatic cancer is being able to find a way to screen for it and detect earlier. One of the main limitations and why there's such a poor survival with this disease is that most people present with very vague symptoms like weight loss, abdominal pain, and back pain. And so, it can go several months before someone is diagnosed. Because of that, a lot of people present with these large tumors that are unresectable or have metastasized to other organs. So, I think a very big need in this disease is identifying patients with early disease when they're still a surgical candidate.

Also, there's been a lot of work recently and will be more work in the future to better understand the genomic profile of everyone’s tumor, so that we can start to do more targeted therapies and individualize care. What we're learning is that between gemcitabine and FOLFIRINOX, some patients will respond to 1 and not the other. So those are some important things, I think that we need in the future and that hopefully, we'll be making some more advances within the next 10 years.