How do you approach adjuvant chemotherapy in patients with resected pancreatic adenocarcinoma?

For my good performance status patients, I offer gem/cap as per the ESPAC-4 trial. Though the incremental benefit is modest, it was statistically significant and the toxicities associated with the combination are quite manageable most of the time. I look forward to the results of three other adjuvant trials: gem vs gem-abraxane, gem vs FOLFIRINOX and gem vs gem + chemoRT.

For resected pancreas cancer - the ESPAC-4 data for gemcitabine/capecitabine support the use of this regimen and outside of a trial setting, this combination represents a new standard option for this disease. We now routinely use this regimen in practice. Nonetheless given pending data on other multi-agent cytotoxic combinations (mFOLFIRINOX, gemcitabine/nab-paclitaxel), the standard may potentially change in the next 1-2 years. An unresolved question is whether (chemo)radiation in addition to systemic therapy should be considered as part of standard adjuvant treatment. The RTOG 0848 trial is ongoing and addresses this question, although results will take a few more years.

The main take away from PRODIGE24 further support the role for adjuvant chemotherapy with an added benefit for FOLFIRINOX. For good performance status patients, I would recommend FOLFIRINOX chemotherapy, which showed a significant improvement in disease free survival and overall survival compared to gemcitabine monotherapy. For those that are not appropriate candidates for FOLFIRINOX, I would still recommend adjuvant capecitabine/gemcitabine based off ESPAC-4. This will potentially change with the results from the APACT trial, which investigated adjuvant gemcitabine/nab-paclitaxel compared to gemcitabine monotherapy, which if positive would be another option for the non-FOLFIRINOX patients.

However, the results from the Dutch trial, which evaluated concurrent chemoradiation for localized disease prior to surgical resection, suggested a clinical benefit compared to those that did not receive radiotherapy. Given the direct for moving adjuvant treatment in the neoadjuvant setting, I would recommend a rule of "6", meaning 6 months total of adjuvant therapy- chemotherapy + concurrent chemoradiation (if they have borderline or locally advanced disease). For example, if a patient was clearly resectable and had up front surgery with no neoadjuvant therapy, I would recommend 6 months of adjuvant chemotherapy (capecitabine/gemcitabine or FOLFIRINOX, depending on their status). Alternatively, if a patient was diagnosed with borderline resectable disease, I would recommend preoperative chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel for 3-4 months followed by concurrent chemoradiation which would total approximately 6 months of treatment) followed by resection with no further adjuvant therapy. When looking into the details of PRODIGE24, the majority of patients did not complete 6 months of adjuvant FOLFIRINOX, hence with chemoradiation, I would be comfortable with 4 months of chemotherapy.