Biliary tract cancer is an aggressive malignancy with a poor prognosis. However, recent studies have found it to be a target-rich disease, with patients benefiting from molecularly driven treatment approaches. Real-life data on the distribution of the targetable genetic aberrations are limited.
In this bicentric, real-world retrospective analysis, we studied the molecular profile and therapy regimes of therapy-refractory patients treated for metastatic biliary tract adenocarcinoma between 2015 to 2021 at two tertiary centers, Medical University of Vienna and University Hospital St. Poelten. Molecular profiling included next-generation sequencing panel, immunohistochemistry, and microsatellite instability (MSI) testing.
In total, included 60 patients, consisting of 27 females and 33 males. The median age at initial diagnosis was 63.0 years (range 34.9-86.3 years). Intrahepatic (n=42) subtype was most common, followed by extrahepatic (n=8), perihilar (n=8) and gallbladder (n=2). The majority of patients (n=42) had an intrahepatic cholangiocarcinoma. In most cases (n=12; 80%), patients had received a platinum-based therapy in first line. We detected a total of 134 genetic aberrations in 48 patients The most frequent mutations affected KRAS (n = 15), TP53 (n = 11), FGFR2 (n=8), IDH2 (n=5), PIK3CA (n=5), NF2 (n=5), IHD1 (n= 4), BRAF (n=4), and CDKN2A (n=4); which together accounted for 45.5% of all mutations. An FGFR fusion gene was detected in one patient. MSI-high status and HER2 positivity were reported in one and two patients, respectively. No genetic aberrations were found in 13 patients. At the time of molecular profiling, 12 patients had actionable mutations half of whom eventually received a targeted therapy. Four of six patients achieved disease control: one complete response, two partial responses and one stable disease.
Based on our analysis, molecular profiling is feasible in tertiary centers and may provide molecular-guided treatment approaches in patients with metastatic biliary tract cancer.
The authors.
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All authors have declared no conflicts of interest.