In a patient with borderline resectable pancreatic adenocarcinoma who received neoadjuvant FOLFIRINOX followed by resection that demonstrated residual disease, how do you proceed in the adjuvant setting?

In order to answer this question completely, I would need to know more about the neoadjuvant FOLFIRINOX that was given. In a patient who received a full 6 months of neoadjuvant therapy followed by successful surgical resection (albeit with poor response), I would not recommend continuing systemic therapy at this time, as there is no literature to support this approach. If there were many positive nodes and/or margins, an argument could be made for chemoradiation in this case, though the literature is mixed regarding the benefit of this strategy.

On the other hand, if the patient had received <6 months of neoadjuvant systemic chemotherapy without any evidence of pathologic response to treatment at resection, I would recommend switching syste...

I agree with the above answer. At this time, there is no evidence that a switch in therapy is going to result in an improvement in outcome, especially if the patient received a total of six months of neoadjuvant FOLFIRINOX. If less than six months of neoadjuvant therapy was received, a switch to gemcitabine and capecitabine based on the ESPAC-4 trial is reasonable, as this combination for six months in the adjuvant setting was shown to improve survival compared to gemcitabine alone after resection.

We have debated this among our disease group. In general we have discounted the pathologic determination of response, and continued with adjuvant FOLFIRINOX despite the discouraging pathologic findings. Could the tumor be relatively radiorefractory and had a response to upfront chemotherapy that was masked by the intervening radiotherapy? Also, I have encountered situations with clear radiologic and biochemical (CA19-9 and CEA) response in which pathology called an absence of response. I am not aware of convincing data regarding pathologic determination of response to neoadjuvant therapy in pancreatic cancer and long-term outcomes.

The other consideration is your alternative. With the negative APACT study, you are left treating with Gem/Cap...

If there was no evidence of response to neoadjuvant chemotherapy would not utilize same regimen in the adjuvant setting. However, based on CT scan sometimes there is response based on 19-9 without radiologic improvement in CT because of fibrosis. Sometimes PET will demonstrate response without CT response. In this setting based on lack of evidence of gem/abraxane in adjuvant setting, would offer gem/capcitabine. Most were surprised about the negative gem/abraxane adjuvant data.