{"entity":{"id":"paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025","kind":"paper","name":"Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial","aka":[],"tldr":"The 2025 Dutch trial in which eight cycles of FOLFIRINOX before surgery, with no treatment afterwards, gave the same survival (about 22 months) as the older gemcitabine chemoradiotherapy schedule, so either can be used but neither is clearly better.","summary":"PREOPANC-2 enrolled 375 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma and WHO performance status 0 or 1 at 19 Dutch centres between June 2018 and January 2021, randomised 1:1 to eight cycles of neoadjuvant FOLFIRINOX followed by surgery without adjuvant treatment (188) or three cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, then surgery and four cycles of adjuvant gemcitabine (187). In the modified intention-to-treat population of 369, after a median follow-up of 42.3 months, median overall survival was 21.9 months with FOLFIRINOX versus 21.3 months with chemoradiotherapy (hazard ratio 0.88, 95 percent confidence interval 0.69 to 1.13, p = 0.32). Grade 3 to 4 neutropenia occurred in 25 versus 22 percent, diarrhoea in 23 versus 1 percent, leukopenia in 8 versus 15 percent; serious adverse events in 49 versus 43 percent; treatment-related deaths two versus one. Registered with EudraCT 2017-002036-17; funded by the Dutch Cancer Society and ZonMw.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2025","url":"https://doi.org/10.1016/S1470-2045(25)00363-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40945523/"},{"label":"Protocol (BMC Cancer 2021)","url":"https://doi.org/10.1186/s12885-021-08031-z"},{"label":"Letter: Neoptolemos and colleagues (Lancet Oncol 2026)","url":"https://doi.org/10.1016/S1470-2045(25)00601-1"}],"tags":["pancreatic-evidence"],"related":["paper-preopanc-preoperative-chemoradiotherapy-jco-2020","paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024","paper-prodige-24-five-year-outcomes-jama-oncol-2022"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy","imrt-igrt"],"targets":[],"drugs":["folfirinox","gemcitabine"],"companies":[],"institutions":["erasmus-mc","amsterdam-umc"],"pathways":[],"terms":["total-neoadjuvant-therapy","neoadjuvant-adjuvant","resectability"],"trials":["preopanc"],"people":["marc-besselink"],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2025,"doi":"10.1016/S1470-2045(25)00363-8","pmid":"40945523","authors":"Janssen QP, van Dam JL, van Bekkum ML, et al.","paperType":"rct","findings":["375 randomised, 369 analysed; neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine chemoradiotherapy plus adjuvant gemcitabine.","Median overall survival 21.9 versus 21.3 months (hazard ratio 0.88, p = 0.32).","Grade 3 to 4 diarrhoea 23 versus 1 percent; serious adverse events 49 versus 43 percent."],"whatItMeans":"Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.","caveats":["No upfront-surgery arm; the comparator was the PREOPANC-1 regimen, not the current adjuvant standard.","The FOLFIRINOX arm received no adjuvant treatment by design.","Letters in the January 2026 issue (Neoptolemos and colleagues; Sherry and colleagues) disputed the design and interpretation."],"participants":375},"route":"/key-papers/paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025/","neighbours":{"paper":[{"id":"paper-prodige-24-five-year-outcomes-jama-oncol-2022","kind":"paper","name":"Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial","route":"/key-papers/paper-prodige-24-five-year-outcomes-jama-oncol-2022/"},{"id":"paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024","kind":"paper","name":"NORPACT-1: neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer","route":"/key-papers/paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024/"},{"id":"paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022","kind":"paper","name":"PREOPANC long-term results: neoadjuvant gemcitabine-based chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer","route":"/key-papers/paper-preopanc-neoadjuvant-chemoradiotherapy-long-term-jco-2022/"},{"id":"paper-preopanc-preoperative-chemoradiotherapy-jco-2020","kind":"paper","name":"Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial","route":"/key-papers/paper-preopanc-preoperative-chemoradiotherapy-jco-2020/"}],"cancer":[{"id":"borderline-resectable-pdac","kind":"cancer","name":"Borderline resectable pancreatic ductal adenocarcinoma","route":"/cancers/borderline-resectable-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"drug":[{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / mFOLFIRINOX","route":"/drugs/folfirinox/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"}],"institution":[{"id":"amsterdam-umc","kind":"institution","name":"Amsterdam UMC / Cancer Center Amsterdam","route":"/institutions/amsterdam-umc/"},{"id":"erasmus-mc","kind":"institution","name":"Erasmus MC Cancer Institute","route":"/institutions/erasmus-mc/"}],"term":[{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"resectability","kind":"term","name":"Resectable, borderline resectable and unresectable","route":"/terms/resectability/"},{"id":"total-neoadjuvant-therapy","kind":"term","name":"Total neoadjuvant therapy (TNT, rectal cancer)","route":"/terms/total-neoadjuvant-therapy/"}],"trial":[{"id":"preopanc","kind":"trial","name":"PREOPANC-1","route":"/trials/preopanc/"}],"person":[{"id":"marc-besselink","kind":"person","name":"Marc G. Besselink","route":"/people/marc-besselink/"}],"bottleneck":[{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"idea":[{"id":"idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease","kind":"idea","name":"Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed","route":"/ideas/idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease/"}]}}