This is the report of a retrospective study aimed to compare survival in patients with advanced cholangiocarcinoma (CCA) harboring alterations matched to targeted drugs, with patients harboring nonactionable alterations. 327 patients were included, 78.9% with intrahepatic CCA (iCCA), 97.9% with chemotherapy for metastatic disease. Actionable molecular alterations per ESCAT (ESMO Scale for Clinical Actionability of Molecular Targets) were identified in 184 patients (56.3%), including IDH1 mutations and FGFR2 fusions (23.1% and 8.0% of iCCA, respectively). Median overall survival in 50 patients with ESCAT I-IV alterations who received matched therapy (48 with iCCA) was 22.6 months (95% CI 20.1-32.8), compared with 14.3 months (95% CI 11.9-18.1) in 130 patients without actionable ESCAT alterations (HR 0.58; 95% CI 0.40-0.85; P=0.005). Among patients receiving matched targeted therapy, median progression-free survival was longer for patients with alterations classified as ESCAT I-II compared with ESCAT III-IV (5.0 vs. 1.9 months; HR 0.36; 95% CI 0.15-0.87; P=0.02). ESCAT represents a tool to guide clinicians in the use of molecular profiling data to choose matched targeted therapies. This study demonstrates that targeted treatment administered per alteration actionability according to ESCAT is associated with improved survival in CCA, particularly in ESCAT I-II iCCA.

(Verdaguer, H. et al., – Clin Cancer Res., April 2022)

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