Adaptive FOLFIRINOX→gem/nab-paclitaxel (plus losartan) drives 88–100% R0 resections in localized pancreatic cancer

The NeoOPTIMIZE study evaluated a “fail-fast” neoadjuvant strategy: 43 resectable/borderline/locally advanced PDAC patients began with four cycles of FOLFIRINOX + daily losartan (angiotensin II receptor blocker antihypertensive).Those showing radiographic or CA-19-9 progression (5/36) or intolerance immediately switched to gemcitabine + nab-paclitaxel for two months, while responders completed eight FFX cycles. After a total of four months of neoadjuvant chemotherapy and restaging, surgery (with or without chemoradiation) achieved R0 margins in 24/27 FFX completers (88%) and 4/4 switchers (100%), resulting in comparable rates of curative resections, regardless of whether early progression forced the switch. Grade ≥3 toxicities were low (7% FFX, 5% GA). Historically, R0 resection rates are around 84% with FOLFIRINOX alone and between 63–85% with up-front gem/nab-paclitaxel, highlighting that the rescue switching strategy preserved—if not improved—surgical quality without adding extra toxicity.