Despite improvements in treatment options, patients with biliary tract cancer (BTC) often have poor outcomes. Only 20% of patients are eligible for surgical resection with curative intent, and <10% of all patients survive past 5 years.1 The British BILCAP trial investigated whether adjuvant capecitabine improved overall survival following surgical resection in patients with BTC, and it established capecitabine as the standard of care in this setting for patients with resected BTC.2,3 At the 2023 ASCO annual meeting, Valerie Crolley, MBBS, MRCP, presented the results from the phase 3 BILCAP trial, which investigated alterations in cancer driver genes and other potentially targetable mutations.2
In this subanalysis, archived fixed formalin paraffin-embedded tissue samples from consented BILCAP patients were collected. DNA and RNA were extracted from these samples, followed by low-pass whole-genome sequencing, targeted gene sequencing, and RNA sequencing for copy number, mutation, and gene fusion analyses.2 A total of 98 patients’ samples were analyzed; 47 had intrahepatic cholangiocarcinoma (CCA), 47 had gallbladder cancer, 2 had distal CCA, and 2 had perihilar CCA.2 In general, a wide variety of driver and potentially actionable mutations were detected, including NTRK1 fusions and amplifications, FGFR1/2/3 fusions, EGFR amplifications, ERBB2 amplifications, MDM2 amplifications, and MET amplifications. The subanalysis demonstrated that most of the alterations investigated in this cohort did not significantly affect recurrence risk or overall survival. FGFR2 fusions had no effect on overall survival (hazard ratio [HR], 0.94; P=.83) or progression-free survival (HR, 0.91; P=.76); however, the presence of FGFR3 fusions and EGFR amplifications significantly reduced overall survival (HR, 5.84; P=.02 and HR, 4.84; P=.01, respectively) and progression-free survival (HR, 4.11; P=.06 and HR, 3.22; P=.03, respectively).2 Although limited by sample size, the researchers concluded that EGFR amplifications and FGFR3 fusions may be important predictive biomarkers in BTC and may serve as a future target for systemic anticancer therapy in patients with BTC.2
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