Choosing Upfront Therapy for Metastatic Pancreatic Cancer

George Kim, MD:The patient has a choice of gemcitabine/Abraxane versus FOLFIRINOX. Those are the 2 standard treatments available in the metastatic setting. How do you go about deciding which treatment is most appropriate for the patient? This really could be a dissertation, but I’ll just try to summarize what’s important. So, our patient has a good performance status. They are in their early 60s. They have a performance status of 1. We’ve corrected their biliary function, meaning we put in a stent. They’re less jaundiced; their liver function as improved.

You have to present to the patient that we have these 2 treatment options. Gemcitabine/Abraxane is given weekly. It does have side effects—the typical myelosuppression, it does cause peripheral neuropathy. You do not necessarily have to put in a port. You don’t have to wear a pump for 48 hours as you do with FOLFIRINOX. Gemcitabine/Abraxane was tested in the United States in the majority of the patients. It was tested in the community. So, the point is that it may be a more amenable combination to use for those patients who are not treated only at academic centers.

In contrast, FOLFIRINOX does require full doses of all the drugs included—oxaliplatin, irinotecan, bolus 5-FU, and leucovorin. So, it is a more intense treatment. Patients do have to wear the pump, they do have to have a portacath placed, and the schedule is every 2 weeks. But typically, patients do have to have an extra couple days after the treatment is given to recover. So, you think about it being every 2 weeks, but they can be out of work, for example, for up to 1 week. Giving a weekly combination of Abraxane/gemcitabine, patients may feel nausea for 1 or 2 days, but are hopefully back to work for the remainder of the week. And, certainly, they can be monitored more closely because the treatments are being given weekly as opposed to administering all the chemotherapy and waiting for the next 2 weeks to see how they do.

Other important considerations are whether folks need a growth factor. So, do you need Neupogen (filgrastim) with a weekly regimen or do you need Neulasta (pegfilgrastim) with FOLFIRINOX? That’s also important when we talk about the cost of the treatments. Supportive care is different in FOLFIRINOX versus gemcitabine/Abraxane, and its supportive care cost can be three-fold as high. Additionally, cost is also important when you talk about gemcitabine/Abraxane versus FOLFIRINOX. Believe it or not, gemcitabine/Abraxane is about $3000 less a month than FOLFIRINOX, which many people would believe is less costly because all the drugs are generic. But, importantly, there is a higher need for supportive care.

In terms of outcome, there is an 11-month survival reported with the FOLFIRINOX regimen as opposed to an 8.7-month benefit with gemcitabine/Abraxane, and so patients will commonly ask: “Which regimen will I get more time with?” But you have to balance that again with the side effects. And if you go back to some of the trial results, you will also see that patients who were given gemcitabine/Abraxane had good performance status and very similar outcomes compared to the 11.7 months seen with FOLFIRINOX. So, they could achieve outcomes as long as 12.6 months. And so, one can argue that in good selective patients—patients with well-controlled symptoms—they can indeed reach the outcomes that are seen with FOLFIRINOX.

We discussed the treatment options with the patient, and we talked about the outcomes of the 2 trials and evaluated the 2 regimens. We talked about the toxicities. We talked about some of the cost and some of the logistics of therapy. Our patient needed to continue to be active. He could not be in the bed or sidelined for long periods of time. He did have a good performance status, an ECOG of 1. And so, all of those factors helped us—the patient and the providers. It’s never just the providers that make that decision, you need the patient’s input. But at the end of the day, it was the patient’s decision to go on to gemcitabine/Abraxane. The patient received 2 months of treatment—2 cycles—and CAT scans were performed, which revealed tumor response. The patient went on for an additional 6 months of therapy, and, again, had stable disease. So, they clearly benefited. Their quality of life was maintained and they were able to manage the toxicities—neutropenia, thrombocytopenia, and neuropathy. All of these symptoms were managed and the patient benefited as he responded, and also had stable disease.

Transcript edited for clarity.

March 2016

• A 63-year-old Caucasian male was admitted to the hospital from the emergency room with symptoms of epigastric pain that radiated toward the back, abdominal distention, vomiting, and jaundice
• Laboratory tests:
  • Bilirubin and liver enzymes; elevated
  • CBC values WNL
  • Hepatitis B, & C testing, negative
  • CEA: 34.2 ng/mL; CA 19-9 > 12000 U/mL
• Performance status, 1
• CT reveals 3.5 cm × 3.7 cm mass in the head of the pancreas and multiple liver nodules; also, indicates an obstruction of the bile duct
• Ultrasound-guided percutaneous needle biopsy of a liver metastases shows adenocarcinoma histology
• The patient undergoes biliary stent placement based on endoscopic retrograde cholangiopancreatogram (ERCP) findings
• Diagnosis: stage IV pancreatic cancer with liver metastasis
• The patient was started with treatment on gemcitabine andnab-paclitaxel
• CT with contrast after two treatment cycles showed marked shrinkage of the pancreatic lesion and liver nodules.
• CT after 6 cycles showed stable disease

November 2016

• The patient reports symptoms of rapid weight loss, abdominal pain, dark urine, and jaundice; he has declining functional status and is often bedridden
• Systemic therapy is under consideration