ASCO 2025 | Phase III trial comparing neoadjuvant mFOLFIRINOX versus PAXG in stage I-III PDAC

Our trial was a Phase III randomized trial comparing what is currently considered one standard of care, that is, the modified FOLFIRINOX regimen, and the other arm was an experimental arm including a four-drug regimen that is called PAXG, including cisplatin, nab-paclitaxel, capecitabine, and gemcitabine. So the trial was addressed to a population of resectable and borderline resectable pancreatic ductal adenocarcinoma. And the trial showed that the new regimen, the PAX-G regimen, prolongs in a significant and clinically meaningful way the event-free survival that was chosen as the primary endpoint of the trial. In particular, the prolongation of median event-free survival was almost six months. And what is more relevant is that the three-year event-free survival was increased from 13% to 31%, so it was more than doubled, with a reduction of the hazard risk of event of 35%, so by 35%. This was significant from a statistical perspective, and in addition to this, we also observed a higher rate of disease control, CA 19-9 response, pathological response, and nodal-negative resection. So I think that there is an internal consistency in this data. Thank you. I think that we should consider this as a new standard. Of course, one concern may be the overall survival data that are not yet mature, but I think we cannot wait for mature data because it will need again a couple of years to have mature data, and actually, we needed to give something to our patients earlier. And I think that maybe it is unlikely that overall survival data will be different from event-free survival data because the internal consistency and the difference between the two arms is so large that it may be unlikely to have different results in terms of overall survival. So I think that patients of this population need to have answers faster than overall survival data can provide. Furthermore, another reason to start with this new regimen tomorrow is that the toxicity profile was better, and the quality of life was better as compared to modified FOLFIRINOX. So we have to abandon this regimen right now. How do you think the best way to improve the best way to achieve three-year event-free survival with the best regimen is around 30%, so of course, we need improvement there, but nowadays, we don’t have new drugs ready for prime time, so what we can do is to try to improve our strategy. One possibility is to consider giving a maintenance therapy after surgery in this population, so we are thinking about planning this kind of trial for the future.