Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer

Author(s): Jaewon Hyung, MD1;Ilhwan Kim, MD2;Kyu-pyo Kim, MD1;Baek-Yeol Ryoo, MD1;Jae Ho Jeong, MD1;Myoung Joo Kang, MD2;Jaekyung Cheon, MD3;Byung Woog Kang, MD4;Hyewon Ryu, MD5;Ji Sung Lee, PhD6,7;Kyung Won Kim, MD8;Ghassan K. Abou-Alfa, MD9,10;Changhoon Yoo, MD1
Source: JAMA Oncol. Published online March 23, 2023. doi:10.1001/jamaoncol.2023.0016
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

A South Korean study showing the superiority of 5FU/LV + liposomal irinotecan vs. 5FU/LV alone. This is an attractive option after gemcitabine + cisplatin, particularly in patients who may not tolerate oxaliplatin due to peripheral neuropathy.


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).


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.


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.


Patients were randomized 1:1 to receive LV, 400 mg/m2, bolus and FU, 2400 mg/m2, for a 46-hour infusion intravenously every 2 weeks with or without nal-IRI, 70 mg/m2, before LV intravenously. Patients were treated until disease progression or unacceptable toxic effects.


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.


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 = .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).


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

Author Affiliations

1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;2Division of Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan,; Republic of Korea3Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of; Medicine, Ulsan, Republic of Korea4Department of Oncology/Hematology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University,; Daegu, Republic of Korea5Division of Hematology and Oncology, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National; University College of Medicine, Daejeon, Republic of Korea6Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine,; Seoul, Republic of Korea7Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul,; Republic of Korea8Asan Image Metrics, Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan; College of Medicine, Seoul, Republic of Korea9Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;10Department of Medicine, Weill Medical College at Cornell University, New York, New York

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