404P - Clinical outcome of patients with advanced biliary tract cancer in a dedicated phase 1 unit

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical Research
Basic Scientific Principles
Presenter Raghav Sundar
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors R. Sundar1, A. Custodio2, J. Lim2, M. Chenard-Poirier2, D. Collins2, S. Kaye2, T.A. Yap2, U. Banerji2, J. Lopez2, J.S. de Bono2
  • 1Drug Development Unit, Institute of Cancer Research ICR, SM2 5PT - London/GB
  • 2Drug Development Unit, Institute of Cancer Research ICR, London/GB



Advanced biliary tract carcinomas (ABC) are fatal malignancies with limited effective therapeutic alternatives for advanced disease. Following first line treatment, clinical trials using experimental novel therapeutic agents may be considered for selected patients. This study describes the experience of ABC patients treated in a specialized phase 1 unit.


Patient characteristics, tumour features, treatment details and clinical outcomes of ABC patients treated at the Drug Development Unit, Royal Marsden Hospital, between 2002 and 2016, were captured and analysed from case and trial records.


123 ABC patients were included in the study, of which 48 patients participated in 41 different phase 1 trials. Patients had a median of 2 previous lines of systemic chemotherapy (range 1 – 6). 8 (17%) entered a second phase 1 study upon progression on the first study. 15 (31%) had molecular characterization of tumours using a targeted panel, yielding 7 potentially actionable mutations including BRCA (2), PIK3CA (2), FGFR, AKT and PTEN loss. However, due to logistical reasons, none of them received treatment on a trial matched to these mutations. Of the 39 evaluable patients, there was one exceptional responder who had a partial response (PR) that continues to be maintained at 1.5 years on a PARP inhibitor study. 18 patients (46%) achieved stable disease (SD) as their best response, and this was sustained for more than 6 cycles (18 weeks) in 4 patients (8%). Median progression free survival was 6.1 weeks (95 %CI 3.3 – 9.3) and median overall survival was 22.0 weeks (95 %CI 18.8 – 25.2). Treatment was generally well tolerated with grade 3 or 4 adverse events only observed in 8 patients (17 %) of which 6 were drug related and led to trial discontinuation in 1 (3%), with no toxicity related deaths.


Experimental phase 1 clinical trials are a reasonable and safe alternative for selected patients with ABC. Several actionable mutations were identified by our targeted panel; however due to logistical reasons none were enrolled onto matched trials. Future work requires more comprehensive molecular profiling to understand the biology underlying the exceptional response, to identify new treatment options, and to match patients in real-time to targeted therapies.

Clinical trial identification


Legal entity responsible for the study

Institute of Cancer Research




All authors have declared no conflicts of interest.