Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit

R. Sundar, A. Custodio, A. Petruckevich, M. Chénard-Poirier, M. Ameratunga, D. Collins, J. Lim, S. B. Kaye, N. Tunariu, U. Banerji, J. de Bono, J. Lopez

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)185-191
Number of pages7
JournalClinical Oncology
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 2018
Externally publishedYes

Keywords

  • Biliary tract cancer
  • developmental therapeutics
  • drug development
  • phase I clinical trial

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