Cholangiocarcinoma

Preliminary evidence suggests that combination treatment with silmitasertib plus gemcitabine/cisplatin as first-line therapy has promising efficacy and a favorable safety profile in patients with locally advanced or metastatic CCA.

A retrospective analysis in a large Chinese patient cohort with bile duct carcinoma indicated that activating IDH1/2 mutations occurred at a lower rate compared with that previously reported in the global population.

This edition of Year in Review is focused on cholangiocarcinoma (CCA), which is a diverse group of malignancies characterized by genomic heterogeneity that potentially drives its pathogenesis. Below is a quick review of some of the topics discussed in this issue, with a focus on recent advances, potentially practice-changing developments, and ongoing challenges in CCA.

Epidemiologic data assessed the incidence rate of FGFR2 gene fusion or rearrangement in Chinese patients with intrahepatic CCA, including those with heterogeneous FGFR2 partner genes.

A retrospective analysis indicated the prognostic value of FGFR2 fusions/rearrangements in patients with intrahepatic CCA receiving systemic chemotherapy, which warrants additional study.

A phase 1/2a, first-in-human clinical study demonstrated that the highly selective, irreversible pan-FGFR inhibitor gunagratinib was safe and well-tolerated in patients with advanced solid tumors, including CCA.

Primary results from the phase 2 FIDES-01 study indicate that derazantinib yields durable objective responses with a manageable safety profile in patients with intrahepatic CCA who harbor FGFR2 fusions/rearrangements.

Interim results of the multicenter, dose-escalation/dose-expansion study indicate that RLY-4008 is well-tolerated, demonstrating selective targeting of FGFR2 and the potential to overcome FGFR inhibitor resistance in patients with advanced CCA.

Retrospective exposure-response analysis data support 20 mg once daily as the starting dose for futibatinib, whereas exposure-safety analysis for futibatinib demonstrated a significant relationship between hyperphosphatemia and futibatinib exposure.