Relapsed or Refractory Metastatic Pancreatic Cancer

John Marshall, MD:If your practice is like mine, you’re watching patients pretty closely. You’re watching markers, you’re doing scans every now and then, and eventually 6 to 8 months into first-line therapy, almost everybody’s cancer will start to grow. And so, we’re looking for this and we find it. When patients progress, we have now a bunch of second-line choices. Now, if you started with gemcitabine/Abraxane or gemcitabine/nab-paclitaxel in frontline therapy, the way I think about it is I want to go to fluoropyrimidine-based therapy second-line. And we’ve got fluoropyrimidine with liposomal irinotecan, a proven second-line regimen. We’ve got conflicting data with fluoropyrimidine/oxaliplatin. We’ve got 1 positive clinical trial, 1 negative clinical trial. And so, I’ve actually shifted some of my enthusiasm from “Everybody’s got to get a FOLFOX” to “Everybody’s got to get a little FOLFIRI” and using more irinotecan-based. But you can do it. There are trials that show you can do it. You can give FOLFIRINOX in the second-line.

No one gives FOLFIRINOX full dose. No one does. We all drop the bolus, we all modify the doses or irinotecan, etc. So, the on-label regimens for FOLFIRINOX are not used practically. When you come to second-line, you also have to be aware of that, modify your doses, and watch your patient closely. I’ve got a patient right now who’s getting second-line FOLFIRINOX after a frontline gemcitabine/nab-paclitaxel. She did very poorly after 4 cycles, but her cancer responded very nicely. So, we’ve essentially gotten her cancer to back off, and now we are resting her with a maintenance approach in the second-line.

In colon cancer, in my world and many other cancers, we, right from the beginning, think about all the different treatments we’re going to give this patient. And we’re even telling patients that, “You’re going to get all these drugs and it’s just, we’re going to play a long chess game and we’re going to move them here and there.” In pancreas cancer, this is a new idea for us because our concept with these patients is just keep you alive, get you off the ledge as fast as we can and try and keep you there—kind of hold on. Well, now we can actually think about lines of therapy in sequence because more and more patients are benefiting from frontline and second-line. We have more and more tools. And so, at least in some patients, particularly our case—low tumor burden, gonna be around through second-line therapy—this is a patient where you think about sequential therapy right from the beginning.

And so, that does influence our decision making. The way I think about it is, you want to play a gemcitabine-based regimen, and you want to play a fluoropyrimidine-based regimen in that patient. You want to make sure you get both of them in at some point along the way. And beyond when and how, I leave that up to the doctor, the situation, the patient in front of you. But part of our challenge is to try and get both of those in so we can get the best survival.

So, this patient has had gemcitabine/nab-paclitaxel, she has now had FOLFIRINOX and has progression of disease, and what next? Well, first, is she a candidate for more treatment? At this point, it’s unusual to see somebody doing well, but that happens; it does happen. The reality is, we don’t have anything routine or standard to give her at this point. Having had FOLFIRINOX, I wouldn’t then try the liposomal irinotecan compound in third-line. I don’t think that’s likely to work any better necessarily than your FOLFIRINOX, and it has some toxicity, so I probably wouldn’t go there.

In our shop, this patient would probably go on to clinical trials. We are looking at more and more new therapies in this space. So, if the patient has a good performance status, is doing okay, what I would recommend is doing a new biopsy on that patient, sending that biopsy for broad molecular profile and see if that patient is eligible for anything in the NCI-MATCH clinical trial or the ASCO-TAPER clinical trial or other studies that are out there.

Transcript edited for clarity.

April 2015

• A 66-year—old female presented to her gastroenterologist with jaundice, weight loss, upper right quadrant abdominal pain, and diarrhea. She continued to carry out normal activity but reported requiring rest on most days.
• CA19-9: 2296 U/ml
• Abdominal CT scan showed an expansive lesion measuring 39 × 26 mm between the pancreas and inferior vena cava, below the portal vein. There was enlarged para-aortic lymph node and stenosis of the common bile duct.
• Endoscopic retrograde cholangiopancreatography was performed and the patient was referred for surgery.
• Explorative laparotomy showed the mass to be inoperable because of local vascular infiltration and liver metastases.
• Pathophysiology confirmed pancreatic adenocarcinoma; stage T4N1M1

May 2015

• The patient was started on gemcitabine + albumin-bound (nab) paclitaxel
• She complained of moderate nausea and fatigue for the first 4 weeks of therapy which was managed with antiemetic therapy
• Neutropenia was managed

August 2015

• CT scan shows stable disease
• CT scan showed no residual liver metastases; the tumor in the head of the pancreas was unchanged in size.
• The patient is asymptomatic and continues to tolerate therapy

June 2016

• Patient hospitalized for high blood glucose levels, diagnoses with new onset insulin-dependent diabetes mellitus
• CT scan showed appearance of several new liver metastases
• The patient was started on the FOLFIRINOX regimen