Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit.
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Embargo End Date
ICR Authors
Authors
Sundar, R
Custodio, A
Petruckevich, A
Chénard-Poirier, M
Ameratunga, M
Collins, D
Lim, J
Kaye, SB
Tunariu, N
Banerji, U
de Bono, J
Lopez, J
Custodio, A
Petruckevich, A
Chénard-Poirier, M
Ameratunga, M
Collins, D
Lim, J
Kaye, SB
Tunariu, N
Banerji, U
de Bono, J
Lopez, J
Document Type
Journal Article
Date
2018-03-01
Date Accepted
2017-11-22
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.
Citation
Clinical oncology (Royal College of Radiologists (Great Britain)), 2018, 30 (3), pp. 185 - 191
Source Title
Publisher
ELSEVIER SCIENCE LONDON
ISSN
0936-6555
eISSN
1433-2981
Research Team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Medicine Drug Development Unit (Kaye)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Medicine Drug Development Unit (Kaye)