Advancing Outcomes in Pancreatic Cancer

George Kim, MD:Exciting studies or news in pancreas cancer is not that common, but I think this year at ASCO, we really have some very important data. This being in the adjuvant setting with the regimen, FOLFIRINOX. The French did a very important study; and they have to be congratulated; using this FOLFIRINOX regimen, which is accepted in the metastatic setting and applying it to the adjuvant setting. In this study, they met their primary endpoint of 3-year disease-free survival. It was 39% versus 21%, and they improved the median by 10 months. The overall survival, a secondary endpoint, was increased to 54 months versus 35 months with the gemcitabine control arm. These are huge numbers, really reflecting important advancement in the treatment of pancreas cancer, but you do have to be careful managing toxicities.

The regimen was not the original FOLFIRINOX regimen; it removed the bolus. They reduced the irinotecan from 180 to 15 mg/m². With this, they still saw a lot of grade 3, grade 4 neutropenia. Particular, they reduced the grade 3, grade 4 neutropenia by about 18%, but they increased the G-CSF use by 17%. I’m not totally convinced that removing a bolus 5-FU is that different. Nonetheless, those changes were made by comparing that to the toxicities that were seen in the metastatic trial. Additionally, they did see about a 50% increase in the diarrhea, grade 3, grade 4 level. Again, with that irinotecan dose reduction, they were able to manage the diarrhea, especially in the first and second cycles, again reflecting the team effort that is needed in managing these patients. You have to stay on top of the neutropenia and the consequences, such as infection. You have to stay on top of the diarrhea and reduce the risks of dehydration and ultimately hospitalization.

This is an important advance in pancreas cancer, and it suggests that we really are able to cure patients with surgery followed by important chemotherapy, that being FOLFIRINOX. We are awaiting data with nab-paclitaxel and gemcitabine also in the adjuvant setting. That trial will hopefully report out maybe at the end of the year. We will hopefully also see improvements in the primary endpoint, which is median disease-free survival. This will allow patients opportunities to choose between an intense regimen versus a regimen that can be given more to everyday patients, certainly out in the community. We’ll have the same decision tree that we have in metastatic disease in the adjuvant setting. Again, this is going to be very important in advancing outcomes in pancreas cancer and ultimately helping our patients.

Now, in terms of experimental therapies, mainly in the metastatic setting, we have a regimen that’s being developed called the NAP-OX regimen. This is bringing Nal-IRI, which is approved in the second line, into frontline, and hopefully this will augment the effects of this combination regimen. This also involves oxaliplatin, also involves infusional 5-FU, and this will hopefully advance the field in the metastatic setting. They’re also planning to use this regimen in the locally advanced borderline setting.

Other interesting research, we still have a lot of work to do in the immunotherapy realm. It’s been a complete disappointment. We have about 2% responses with checkpoint inhibitors, again, just highlighting that we need to look for Lynch syndrome or MSI-high, as those patients will benefit. There has to be more work. It’s likely going to be in combination with vaccines or other immunomodulating therapies. I know that ibrutinib; that agent will be reported out. We have a lot of work to do. Other targets include stem cell inhibition, targeting the stroma, and also the important work that’s being done withBRCAandBRCA-like, and homologous DNA repair defects. We have to identify who those patients are that potentially will benefit from PARP inhibitors. Right now, there’s a lot of excitement and a lot of hope in pancreatic cancer which we didn’t have about a year ago. Certainly, with the early-stage disease from FOLFIRINOX, and then also some of the trials that will hopefully read out and be positive in the coming months. A lot of reason for optimism in the treatment of pancreatic cancer.

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