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
Enhertu shows promising activity in met-BTC’s that are HER2-pos but also in HER2-low. Using this in HER2-low would be off label but something to consider after SOC therapy.
HER2 is a target we should be considering in BTC’s starting in the first line. The overall response rates were 80% with 55% having a CR/PR. Interestingly it seems HER2 is much more prevalent in GBC compared to cholangio’s, at least in this study.
A Phase II basket study looking at tucatinib + trastuzumab in mBTC, only 30 patients were studied as this is a small subpopulation. However, the results were compelling, with an ORR of 47%. For a 3L patient who has failed gem/cis and FOLFONI, this would be a targeted option to consider.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
