TY - JOUR
T1 - Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit
AU - Sundar, R.
AU - Custodio, A.
AU - Petruckevich, A.
AU - Chénard-Poirier, M.
AU - Ameratunga, M.
AU - Collins, D.
AU - Lim, J.
AU - Kaye, S. B.
AU - Tunariu, N.
AU - Banerji, U.
AU - de Bono, J.
AU - Lopez, J.
N1 - Funding Information:
R. Sundar was supported by the National Medical Research Council (NMRC) , Singapore (NMRC/Fellowship/ 0026/2015 ). The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK. Support is also provided by the Experimental Cancer Medicine Centre (to The Institute of Cancer Research) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research).
Publisher Copyright:
© 2017 The Royal College of Radiologists. Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Biliary tract cancer
KW - developmental therapeutics
KW - drug development
KW - phase I clinical trial
UR - http://www.scopus.com/inward/record.url?scp=85041689963&partnerID=8YFLogxK
U2 - 10.1016/j.clon.2017.11.011
DO - 10.1016/j.clon.2017.11.011
M3 - Article
C2 - 29224898
AN - SCOPUS:85041689963
SN - 0936-6555
VL - 30
SP - 185
EP - 191
JO - Clinical Oncology
JF - Clinical Oncology
IS - 3
ER -