Molecular profiling and matched targeted treatment in cholangiocarcinoma: results from the Italian dataset (ANITA)
Menée en Italie dans un contexte de vie réelle à partir de données portant sur 621 patients atteints d'un cholangiocarcinome de stade avancé, cette étude de cohorte évalue l'intérêt d'un profilage moléculaire pour aider à choisir une thérapie ciblée personnalisée
Background and Aims: Extended molecular profiling (EMP) is recommended to tailor targeted treatment for advanced cholangiocarcinoma (CCA). However, neither the impact of EMP nor the availability of targeted therapies has been extensively described in a real-world setting.
Methods: ANITA is an observational (retrospective and prospective) study enrolling 621 patients with CCA from 10 tertiary Italian cancer centers between 2017 and 2023. Current analyses are focused on access to EMP, evolving rate of EMP over time, access to as well as outcomes with targeted treatment. Moreover, we explore the prognostic and predictive role of major driver molecular alterations.
Results: EMP was performed in 79.9% of the patients with advanced CCA. EMP rate significantly increased over the years (2017 to 2023: +25.8%): 139 patients with ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) I-III alterations were identified and 18.7% received matched tailored therapies. No differences were seen in overall survival (OS) and progression-free survival (PFS) according to EMP availability. Patients receiving targeted treatments reported the best OS, significantly longer than those untreated with targeted therapies (HR 0.49, 95% CI 0.28-0.86) or without EMP available (HR 0.34, 95% CI 0.21-0.54). Among ESCAT I-III positive cases, 42 had FGFR2-fused/rearranged and 59 had IDH1-mutated disease: after excluding patients treated with targeted treatment, only FGFR2 fusions/rearrangements confirmed their prognostic role for OS.
Conclusions: Despite a broader availability of EMP in advanced CCA, patient access to targeted treatments remains suboptimal. Our results demonstrate that such treatments can dramatically impact on OS, Therefore, strategies aiming at increasing the access to (and accelerate the availability of) targeted treatments are warranted.
Journal of Hepatology , résumé, 2026