In patients with biliary tract cancer, EGFR amplifications and FGFR3 fusions may serve as important predictive biomarkers and as potential targets for anticancer therapy in the future.
Patients with biliary tract cancer (BTC) often have poor outcomes despite improvements in treatment options. 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 study examined whether adjuvant capecitabine improved overall survival after 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 Valerie Crolley, MBBS, MRCP, presented the results from an analysis of the phase 3 BILCAP trial, which investigated alterations in cancer driver genes and other potentially targetable mutations, at the 2023 ASCO annual meeting.2
Valerie Crolley, MBBS, MRCP, presented the results from an analysis of the phase 3 BILCAP trial, which investigated alterations in cancer driver genes and other potentially targetable mutations, at the 2023 ASCO annual meeting.2
Archived fixed formalin paraffin–embedded tissue samples from consented BILCAP patients were collected in this analysis. 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 sub-analysis showed that the majority of the alterations investigated in this cohort did not significantly affect recurrence risk or overall survival (OS). FGFR2 fusions had no effect on OS (hazard ratio [HR], 0.94; P=.83) or progression-free survival (PFS; HR, 0.91; P=.76); however, the presence of FGFR3 fusions and EGFR amplifications significantly reduced OS (HR, 5.84; P=.02 and HR, 4.84; P=.01, respectively) and PFS (HR, 4.11; P=.06 and HR, 3.22; P=.03, respectively).2 Despite sample-size limitations, 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
References
- Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663-673.
- Crolley V, Guest R, Beggs A, et al. Investigating alterations in cancer driver genes and other potentially targetable mutations in patients with intrahepatic cholangiocarcinoma (iCCA) treated on the randomized phase III multi-centre BILCAP clinical trial. Presented at: ASCO 2023 Annual Meeting, June 2-6, 2023; Chicago, IL.
- Kelley RK, Bridgewater J, Gores GJ, Zhu AX. Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol. 2020;72(2):353-363.