{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:44:05Z","timestamp":1793781845862,"version":"4.6.1"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"Importance<\/jats:title>The NIFTY trial demonstrated the benefit of treatment with second-line liposomal irinotecan (nal-IRI) plus fluorouracil (FU) and leucovorin (LV) for patients with advanced biliary tract cancer (BTC).<\/jats:p><\/jats:sec>Objective<\/jats:title>To report the updated efficacy outcomes from the NIFTY trial with extended follow-up of 1.3 years with reperformed masked independent central review (MICR) with 3 newly invited radiologists.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>The NIFTY trial was a randomized, multicenter, open-label, phase 2b clinical trial conducted between September 5, 2018, and December 31, 2021, at 5 tertiary referral centers in South Korea. Patients with advanced BTC whose disease progressed while receiving first-line gemcitabine plus cisplatin with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1, were eligible. Data analysis was completed on May 9, 2022.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomized 1:1 to receive LV, 400 mg\/m2<\/jats:sup>, bolus and FU, 2400 mg\/m2<\/jats:sup>, for a 46-hour infusion intravenously every 2 weeks with or without nal-IRI, 70 mg\/m2<\/jats:sup>, before LV intravenously. Patients were treated until disease progression or unacceptable toxic effects.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Primary end point was progression-free survival (PFS) as assessed by MICR. Secondary end points were PFS as assessed by the investigator, overall survival, and objective response rate.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 178 patients (75 women [42.1%]; median [IQR] age, 64 [38-84] years) were randomly assigned, and 174 patients were included in the full analysis set (88 patients [50.6%] in the nal-IRI plus FU\/LV group vs 86 patients [49.4%] in the FU\/LV alone group). In this updated analysis, the median MICR-assessed PFS was 4.2 months (95% CI, 2.8-5.3) for the nal-IRI plus FU\/LV group and 1.7 months (95% CI, 1.4-2.6) for the FU\/LV alone group (hazard ratio, 0.61; 95% CI, 0.44-0.86; P<\/jats:italic>\u2009=\u2009.004), in contrast to the 7.1 and 1.4 months reported in the previous study, respectively. The discordance rate for tumor progression date between the MICR and investigators was 17.8% (vs 30% in the previous study).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The NIFTY randomized clinical trial demonstrated significant improvement in PFS with treatment with nal-IRI plus FU\/LV compared with FU\/LV alone for patients with advanced BTC after progression to gemcitabine plus cisplatin. The combination of nal-IRI plus FU\/LV could be considered as a second-line treatment option for patients with previously treated advanced BTC.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>clinicaltrials.gov Identifier: NCT03524508<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2023.0016","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T15:01:49Z","timestamp":1679583709000},"page":"692","source":"Crossref","is-referenced-by-count":94,"title":["Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Jaewon","family":"Hyung","sequence":"first","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of 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