{"entity":{"id":"paper-napoli-1-nanoliposomal-irinotecan-lancet-2016","kind":"paper","name":"Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial","aka":[],"tldr":"The 2016 trial that gave patients whose pancreatic cancer had grown through gemcitabine a proven second treatment: liposomal irinotecan with fluorouracil lengthened survival from about four to six months.","summary":"NAPOLI-1 randomised 417 patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy at 76 sites in 14 countries between January 2012 and September 2013 to nanoliposomal irinotecan plus fluorouracil and folinic acid (117, an arm added by amendment), nanoliposomal irinotecan alone (151) or fluorouracil and folinic acid (149). After 313 events, median overall survival was 6.1 months with the combination against 4.2 months with fluorouracil and folinic acid (hazard ratio 0.67, 95 percent confidence interval 0.49 to 0.92, p = 0.012); monotherapy did not differ from control (4.9 versus 4.2 months, hazard ratio 0.99). The commonest grade 3 or 4 events with the combination were neutropenia (27 percent), fatigue (14 percent), diarrhoea (13 percent) and vomiting (11 percent). Funded by Merrimack Pharmaceuticals; the drug is now marketed by Ipsen.","asOf":"2026-09-24","links":[{"label":"Lancet 2016","url":"https://doi.org/10.1016/S0140-6736(15)00986-1"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26615328/"},{"label":"ClinicalTrials.gov NCT01494506","url":"https://clinicaltrials.gov/study/NCT01494506"}],"tags":["pancreatic-evidence"],"related":["paper-napoli-3-lancet-2023","paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["topoisomerase-inhibitors","cytotoxic-chemotherapy"],"targets":[],"drugs":["liposomal-irinotecan","fluorouracil","nalirifox"],"companies":["ipsen"],"institutions":[],"pathways":[],"terms":["os","hazard-ratio"],"trials":["napoli-3"],"people":["daniel-von-hoff"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2016,"doi":"10.1016/S0140-6736(15)00986-1","pmid":"26615328","authors":"Wang-Gillam A, Li CP, Bodoky G, et al.","paperType":"rct","findings":["417 patients after gemcitabine-based therapy; three arms.","Median overall survival 6.1 versus 4.2 months for the combination against fluorouracil and folinic acid (hazard ratio 0.67).","Nanoliposomal irinotecan alone gave no benefit (4.9 versus 4.2 months, hazard ratio 0.99).","Grade 3 or 4 neutropenia 27 percent, fatigue 14 percent, diarrhoea 13 percent."],"whatItMeans":"The first approved second-line regimen and the basis of NALIRIFOX, which NAPOLI 3 later moved to first line; it fixed the sequence (gemcitabine-based first, then liposomal irinotecan with fluorouracil) written into the 2018 ASCO guideline.","caveats":["Open-label; the combination arm was added mid-trial by protocol amendment.","A gain of about two months in a population with a median survival under six."],"changedPractice":true,"participants":417},"route":"/key-papers/paper-napoli-1-nanoliposomal-irinotecan-lancet-2016/","neighbours":{"paper":[{"id":"paper-conroy-folfirinox-pancreatic-nejm-2011","kind":"paper","name":"Conroy 2011: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer (PRODIGE 4/ACCORD 11)","route":"/key-papers/paper-conroy-folfirinox-pancreatic-nejm-2011/"},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/"},{"id":"paper-napoli-3-lancet-2023","kind":"paper","name":"NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer","route":"/key-papers/paper-napoli-3-lancet-2023/"}],"cancer":[{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"liposomal-irinotecan","kind":"drug","name":"Liposomal irinotecan","route":"/drugs/liposomal-irinotecan/"},{"id":"nalirifox","kind":"drug","name":"NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)","route":"/drugs/nalirifox/"}],"company":[{"id":"ipsen","kind":"company","name":"Ipsen","route":"/companies/ipsen/"}],"term":[{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"trial":[{"id":"napoli-3","kind":"trial","name":"NAPOLI 3","route":"/trials/napoli-3/"}],"person":[{"id":"daniel-von-hoff","kind":"person","name":"Daniel D. Von Hoff","route":"/people/daniel-von-hoff/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}],"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/"}]}}