Igor Astsaturov, MD, PhD

This trial demonstrates better efficacy of modified FOLFIRINOX compared with gemcitabine as adjuvant therapy for previously resected pancreatic adenocarcinoma. The trial reached its intended endpoint and showed improved OS in the experimental arm with quite impressive median survival of 54.4 months.

The control arm of the study gemcitabine alone is no longer recognized as the standard of care since the release of the ESPAC4 trial in the U.K., which showed a 28-month median OS in gemcitabine plus capecitabine arm. In ESPAC-4, the control arm of gemcitabine showed inferior survival of only 25.5 months, which may be due to the differences in the patient populations, including the percentage of patients with positive margins who apparently did not benefit much from the gemcitabine plus capecitabine regimen in the subset analysis of ESPAC-4.

It will be very interesting to understand the factors contributing to such impressive results in the FOLFIRINOX arm, which is an undoubtedly a very effective, albeit toxic, chemotherapy regimen. In the U.S., many centers follow the strategy of maximizing neoadjuvant therapy due to understanding of pancreatic cancer as of a systemic disease. This also helps avoiding unnecessary surgeries and surgeries with positive margins where no therapy provides appreciable survival benefit. Considering the results of the study by Conroy and colleagues, this trial is impressive and confirmatory of FOLFIRINOX being a very effective chemotherapy regimen now applicable in the adjuvant setting for resected pancreatic cancer. 

Reference:

Neoptolemos JP, et al. Lancet. 2017;doi:10.1016/S0140-6736(16)32409-6.

Allyson Ocean, MD

This is a very important potential new standard of care for patients with resectable pancreatic cancer because of the significant improvement in survival outcomes. The challenge will be the delivery of this regimen to patients after they undergo the extensive surgery required for pancreatic cancer. Patients are debilitated after surgery, and it is hard to get in a regimen such as FOLFIRINOX, but it can be done.

The median survival improvement of 54 months vs. 35 months with gemcitabine alone is the most we have seen in a long time. I was surprised this presentation was not included in the plenary session because of the significance of the data in this disease, where outcomes are so poor. This is an extremely important survival improvement that is very encouraging news for patients able to have surgery.

The other thing to keep in mind, however, is the comparator arm was gemcitabine alone and we have not used gemcitabine alone as adjuvant therapy for many years now. The standard of care today is gemcitabine plus capecitabine.

We now need to figure out how we can get more patients to surgery so they can be treated with this new treatment regimen. FOLFIRINOX should become the new standard of care following resection among patients with pancreatic cancer. However, the application of the regimen may be difficult, so we need to think about this in our patient subgroups, because not all patients will be able to handle such a regimen. I also would now like to see what the response is for patients with BRCA mutations in pancreatic cancer using FOLFIRINOX in the adjuvant setting.