Frontline Options for the Treatment of Pancreatic Cancer

George Kim, MD:The factors in deciding which treatment to administer, either FOLFIRINOX or gemcitabine/nab-paclitaxel are, as we described, what does the patient want, or is willing to tolerate, in terms of toxicity. Both regimens do cause neuropathy. They cause low platelets, and then there’s the challenge of what we do sequentially. What treatment do we have available that is FDA-approved, category 1—recommended in the second line? So, that’s why I think more and more we’re using gemcitabine/nab-paclitaxel in the frontline setting, and then proceeding to 5-FU-based therapy with Nal-IRI (nanoliposomal irinotecan).

Now, the patient is 57 years of age, and we also have to incorporate that into our decision making. We should back up and remind ourselves that is a relatively young age for development of pancreatic cancer. The average age is right around 72. So, this patient has developed an early pancreatic cancer. We want to know if there are any important hereditary syndromes, such asBRCA, or Lynch syndrome that we need to consider. There are treatments such as PARP inhibitors or checkpoint inhibitors respectively for those syndromes. Looking at his comorbidities, he has hypertension, he has glucose intolerance, not frank diabetes. He’s not requiring insulin obviously, but we want to monitor that and focus on, if there are any aberrations, correcting them appropriately.

Now, this patient is 57, he’s probably still working. We need to think about some of the logistical issues of our regimens. Giving FOLFIRINOX is associated with having to wear a pump, giving a port, and typically patients that have to work, they’ll come in on a Wednesday, have the pump disconnected on a Friday, try to rest up through the weekend, and get back to work on Monday or Tuesday. We contrast that with nab-paclitaxel/gemcitabine which is given weekly. It allows us to monitor the patient closely. We’ll treat them on a Friday, they’ll come in, go home, recover Saturday, Sunday and be back to work on Monday. Then we can determine the following Friday whether they should continue with treatment or whether there are reasons, such as neutropenia or neuropathy, that don’t allow the weekly therapies. There’s a little more opportunity to adjust the doses with the gemcitabine/nab-paclitaxel regimen. And that may be important, again, for a person that needs to work, that does not want to be burdened by the pump; so very important.

Transcript edited for clarity.

A 57-Year-Old Man With Abdominal Pain and Unexplained Weight Loss

• A 57-year-old man was referred from his primary care clinician with complaints of persistent pain in his upper abdomen that radiate to his back
• History
  • Former smoker (35 years, quit 5 years ago)
  • Was obese (BMI 29.0), but began losing weight despite not changing his eating habits
  • Reports feeling “tired” despite regular sleep habits
  • Treated for DVT 8 months ago
  • Hypertension controlled on medication, impaired glucose tolerance
  • Family history: mother alive with type 2 diabetes, father died (MI)
• Clinical evaluation
  • CT reveals mass in head of pancreas with metastases in liver and blood vessels
  • CA19-9 level: 55 times upper limit of normal
  • ECOG PS: 1
• Diagnosis: unresectable metastatic pancreatic cancer
• Patient began treatment with IV nab-paclitaxel (125 mg/m²) plus IV gemcitabine (1000 mg/m²) on days 1, 8 and 15 of a 28-day cycle
  • Experienced grade 3 neutropenia; did not require growth factors
  • Had mild peripheral neuropathy that did not progress or require dose adjustment
• At 6 months, patient progressed and received second-line treatment with liposomal irinotecan in combination with 5-FU/LV