Molecular profiling and matched targeted treatment in cholangiocarcinoma: Results from the Italian dataset (ANITA)

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.

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 rates of EMP over time, access to targeted treatments and respective outcomes. Moreover, we explore the prognostic and predictive role of major driver molecular alterations.

EMP was performed in 79.9% of patients with advanced CCA. The rate of EMP increased significantly over time (2017-2023: +25.8%). Overall, 139 patients harbored ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) I-III alterations, and 18.7% of these patients received matched targeted therapies. No differences were seen in overall survival (OS) and progression-free survival (PFS) according to EMP availability. Patients receiving targeted therapies had the best OS, which was significantly longer than that of patients who did not receive targeted treatments (hazard ratio 0.49, 95% CI 0.28-0.86) or those without EMP available (hazard ratio 0.34, 95% CI 0.21-0.54). Among ESCAT I-III-positive cases, 42 patients had FGFR2 fusions/rearrangements and 59 had IDH1 mutations. After excluding patients treated with targeted therapies, only FGFR2 fusions/rearrangements retained a prognostic association with OS.

Despite the increasing availability of EMP in advanced CCA, patient access to targeted therapies remains suboptimal. Our findings demonstrate that targeted treatments can markedly improve OS. Therefore, strategies to increase access to - and accelerate the availability of - targeted therapies are warranted.

ANITA is the largest observational, retrospective and prospective, study exploring the impact of molecular profiling and matched targeted treatment in a large cohort of patients with advanced cholangiocarcinoma. While the availability of molecular profiling has increased in recent years, access to targeted therapy is still limited in routine practice. Administration of targeted treatment has a significant impact on overall survival, highlighting the importance of promoting timely and early access to new agents in this disease.

ESR-21-21387.