Nanoliposomal irinotecan in advanced biliary tract cancers

The treatment of advanced biliary tract cancers remains a challenge. In the past 15 years, however, things have finally begun to move. The combination of cisplatin, gemcitabine (CISGEM regimen), and immune checkpoint inhibitors became the first-line standard, pushing median survival beyond 1 year. 1 Oh DY Ruth He A Qin S et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022; 1EVIDoa2200015 Crossref PubMed Google Scholar , 2 Kelley RK Ueno M Yoo C et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401: 1853-1865 Summary Full Text Full Text PDF PubMed Scopus (158) Google Scholar Advanced biliary tract cancers also entered the era of targeted therapy, opening the way to a new range of effective treatments. 3 Mosele F Remon J Mateo J et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020; 31: 1491-1505 Summary Full Text Full Text PDF PubMed Scopus (660) Google Scholar However, apart from an actionable genetic alteration, treatment options remain limited beyond the first-line setting. The ABC-06 phase 3 trial established FOLFOX (fluorouracil, leucovorin, and oxaliplatin) as the standard second-line treatment, but with limited overall survival benefit over best supportive care alone (median 6·2 months [95% CI 5·4–7·6] vs 5·3 months [4·1–5·8], hazard ratio [HR] 0·69 [0·50–0·97]; p=0·031). 4 Lamarca Á Palmer DH Wasan H et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021; 22: 690-701 Summary Full Text Full Text PDF PubMed Scopus (399) Google Scholar Nanoliposomal irinotecan and fluorouracil plus leucovorin versus fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies (AIO NALIRICC): a multicentre, open-label, randomised, phase 2 trialThe addition of nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve progression-free survival or overall survival and was associated with higher toxicity compared with fluorouracil plus leucovorin. Further research is necessary to define the role of irinotecan-based combinations in second-line treatment of biliary tract cancer. Full-Text PDF Open Access