EXTENDED molecular profiling and matched targeted treatment were associated with significantly improved overall survival in patients with advanced cholangiocarcinoma, according to real-world data from the Italian ANITA study.
Why Molecular Profiling Matters in Cholangiocarcinoma
Cholangiocarcinoma is a rare and aggressive biliary tract cancer with limited treatment options and a poor prognosis, particularly in advanced disease. Recent advances in precision oncology have highlighted the importance of molecular profiling to identify actionable genetic alterations that may guide targeted therapies, as recommended by the European Society for Medical Oncology.
However, while molecular profiling has increasingly been incorporated into clinical guidelines, its real-world impact on outcomes and access to targeted treatment has remained unclear.
Study Design and Patient Population
The ANITA study was an observational, retrospective and prospective analysis enrolling 621 patients with cholangiocarcinoma from 10 tertiary cancer centres in Italy between 2017–2023. Investigators assessed access to extended molecular profiling, trends over time, availability of targeted therapies, and survival outcomes in routine clinical practice.
Increasing Access to Molecular Profiling Over Time
Extended molecular profiling was performed in 79.9% of patients with advanced cholangiocarcinoma. Importantly, the rate of molecular profiling increased significantly over the study period, rising by 25.8% between 2017 and 2023.
Among those tested, 139 patients were identified as harbouring actionable alterations classified as ESCAT I–III, including FGFR2 fusions or rearrangements and IDH1 mutations.
Limited Access to Targeted Treatment
Despite broader availability of molecular profiling, access to targeted treatment remained limited. Only 18.7% of patients with ESCAT I–III alterations ultimately received matched targeted therapies, highlighting a substantial gap between identifying actionable mutations and delivering precision treatment in clinical practice.
No significant differences in overall survival or progression-free survival were observed based on molecular profiling alone when targeted treatment was not administered.
Targeted Treatment Significantly Improved Survival
Patients who received matched targeted treatment experienced the most favourable outcomes. Overall survival was significantly longer compared with patients who did not receive targeted therapy or those who did not undergo molecular profiling.
The study reported a near 50% reduction in the risk of death among patients treated with targeted agents, demonstrating the clear clinical benefit of precision treatment when access was achieved.
Prognostic Value of Key Molecular Alterations
Among patients with ESCAT I–III alterations who did not receive targeted treatment, FGFR2 fusions or rearrangements retained an independent prognostic role for overall survival. In contrast, IDH1 mutations did not demonstrate a significant prognostic impact in this untreated subgroup.
Clinical Implications and Future Directions
While molecular profiling in cholangiocarcinoma has become more widely available, the study demonstrated that access to targeted treatment remains suboptimal in routine practice. The authors concluded that strategies to promote earlier and broader access to targeted therapies are urgently needed, as these treatments can dramatically improve survival outcomes for patients with advanced disease.
Reference
Genovesi V et al. Molecular profiling and matched targeted treatment in cholangiocarcinoma: results from the Italian dataset (ANITA). J Hepatol. 2025;doi:10.1016/j.jhep.2025.12.016.
