Targeted therapy could improve the survival of patients diagnosed with biliary tract cancers (BTCs) with therapeutically actionable or potentially actionable gene alterations, according to a new study presented at the Cholangiocarcinoma Foundation Annual Conference. BTCs include intrahepatic, perihilar, and distal cholangiocarcinoma (CCA), as well as gallbladder cancer.

“Several molecular profiling studies have identified potentially actionable aberrations in subsets of BTCs but potential efficacy of molecularly matched therapies in advanced BTCs has not been analyzed yet,” the authors said.

Therefore, the research team from the University of Michigan in Ann Arbor and the Howard Hughes Medical Institute in Chevy Chase, Maryland analyzed genomic data from 124 patients (median age, 59 years, age range, 17-80 years) with advanced BTC.

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Most (71%) patients had intrahepatic CCA, followed by gallbladder cancer (10.4%), perihilar and distal CCA (8% and 6.4%, respectively), and mixed hepatocellular/CCA (4%). Data analyzed included mutations, copy number alterations, gene fusions, and pathogenic germline variants.

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They classified genetic alterations as actionable, ie, predictive of response to a US Food and Drug Administration (FDA) approved drug(s), or potentially actionable, ie, associated with potential responsiveness to experimental drugs based on data from clinical trials or preclinical evidence.

Fifty-four patients harbored actionable mutations. Of those, 18 received matched targeted therapy. This group of patients showed improved overall survival when compared with patients who did not receive targeted therapy or those without actionable mutations (23.5 vs 14.4 vs 14.6 months).

Actionable mutations that may be matched with FDA approved therapeutics included IDH1/IDH2 mutations (n=23), FGFR2/ FGFR3 fusions (n=15), BRAF V600E mutation (n=4), BRCA1/2 (n=4), ERBB2 amplification (n=4), and KRAS G12C (n=3). It also included patients with high tumor mutational burden (>10 mutations/megabase, n=2) and microsatellite instability (n=1).


Kumar-Sinha C, Vats P, Tran N, et al. Genomics driven precision oncology in advanced biliary tract cancer (BTC) improves survival. Poster presented at: Cholangiocarcinoma Foundation Annual Conference: February 23-25, 2022; Salt Lake City, Utah.