Exploring Different Treatment Options for Biliary Tract Cancer

Treatment approaches for biliary tract cancers have evolved significantly, with first-line therapy traditionally centered on cytotoxic chemotherapy regimens. The standard of care has been gemcitabine with cisplatin, which demonstrated superior outcomes compared with gemcitabine monotherapy and earned National Comprehensive Cancer Network Category 1 recommendation status. Recent advances have incorporated immunotherapy into frontline treatment, with chemo-immunotherapy combinations using gemcitabine and cisplatin as the backbone along with checkpoint inhibitors like durvalumab and pembrolizumab becoming preferred options for eligible patients. Alternative first-line regimens include other gemcitabine-based combinations with partners like nab-paclitaxel, or fluoropyrimidine-based regimens such as FOLFOX and CAPOX. For patients with specific molecular alterations, targeted therapies may be considered in the first-line setting, including IDH inhibitors and potentially RET inhibitors for patients with mutation-positive disease.

Second-line treatment options focus heavily on targeted therapies based on identified molecular alterations, with FOLFOX being a preferred chemotherapy regimen specifically studied in the subsequent-line setting. Other options include fluoropyrimidine-based regimens like FOLFIRI, fluorouracil with oxaliplatin or irinotecan, and regorafenib. The targeted therapy landscape includes BRAF inhibitors for BRAF V600E mutations, multiple FGFR inhibitors for FGFR2 fusions, IDH inhibitors for IDH1 mutations, and HER2-directed therapies for ERBB2 alterations or amplifications.

FGFR2-targeted therapy represents a particularly important treatment area unique to biliary tract cancers, with pemigatinib and futibatinib showing the most robust clinical data. Pemigatinib, a selective FGFR1-3 inhibitor, demonstrated a 35% overall response rate and 6.9-month median progression-free survival in the FIGHT-202 trial. Futibatinib, an irreversible FGFR1-4 inhibitor, showed superior efficacy with a 42% objective response rate, 9.7-month median duration of response, and 9-month progression-free survival. These agents require careful monitoring for unique adverse effects, particularly hyperphosphatemia, dermatologic and nail toxicities, stomatitis, and rare ocular complications.