Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit.
de Bono, J
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Aims Advanced biliary tract carcinomas (ABC) are malignancies with limited effective therapies for advanced disease. There is little published evidence of outcomes of ABC patients participating in phase I clinical trials.Materials and methods Patient characteristics, treatment details and outcomes of ABC patients treated at a dedicated phase I unit were captured and analysed from case and trial records.Results In total, 123 ABC patients were included in the study, of which 48 patients participated in 41 different phase I trials; 75 (61%) did not participate due to rapid disease progression or patient choice. Molecular characterisation of tumours using a targeted panel was conducted in 15 (31%), yielding several potentially actionable mutations, including BRCA, PIK3CA, FGFR, AKT and PTEN loss. Of the 39 evaluable patients there was one exceptional responder. Eighteen (46%) other patients achieved stable disease as their best response, with a clinical benefit rate at 4 months of 10%. Treatment was generally well tolerated with grade 3 or 4 adverse events only observed in eight patients (17 %), of which six were drug related and led to trial discontinuation in one (3%), with no toxicity-related deaths.Conclusion Carefully selected ABC patients have been found to tolerate experimental phase I clinical trials without excess toxicity. The aggressive nature of this disease warrants consideration of early referral to a phase I unit. Future work will require comprehensive molecular profiling in an attempt to understand the biology underlying the exceptional responders and to match patients in real-time to targeted therapies.
Biliary Tract Neoplasms
Antineoplastic Combined Chemotherapy Protocols
Clinical Trials, Phase I as Topic
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Medicine Drug Development Unit (Kaye)
License start date
Clinical oncology (Royal College of Radiologists (Great Britain)), 2018, 30 (3), pp. 185 - 191