Advanced biliary tract cancers (aBTCs) are heterogeneous diseases with a median overall survival (OS) < 1year. Platinum-based chemotherapy doublets are the frontline standard-of-care. Increasing evidence points out the strong addiction of aBTCs to druggable oncogenic alterations. We assessed the success rate and the clinical benefit of administering molecular targeted agents (MTAs) based on the molecular alterations found in patients with aBTCs.
Patients with aBTCs were prospectively enrolled in our prospective molecular screening program (MOSCATO 01). An on-purpose tumor biopsy was performed for each patient, followed by high-throughput molecular analysis. Patients were then guided to MTAs matching the molecular alterations. The primary endpoint was progression-free survival (PFS), with clinical benefit defined by a PFS ratio (PFS [MTA]/PFS [prior line]) >1.3.
From November 2011 to March 2016, among 1036 adult patients included in the MOSCATO-01 trial, 48 biopsy procedures were performed in 43 patients (4%) with aBTC (4 patients re-included, one 3 times).Thirty three patients (77%) had intrahepatic cholangiocarcinoma. Patients had failed a median of 2 previous lines (range, 1-5). Successful biopsy procedures and DNA extractions enabled molecular analysis in 38 samples (79%), and at least one molecular alteration was detected in 35 samples (71%). Following analysis, 25 patients could be orientated to an appropriate early clinical trial or accessible MTA (25/38, 66%), and 19 patients could be treated on the basis of molecular alterations (19/38, 50%). For the biology-driven treatment group, The PFS ratio was 1.52 [0.08, 7.1]. Six patients (32%) had an objective response (complete [CR] or partial [PR] response), 16 (84%) had a clinical benefit (stable disease+PR+CR), and 7 (37%) had a PFS≥6 months. This strategy led to a significant overall survival improvement compared to patients who were not treated according to their tumor molecular characterization (HR = 0.26 [95%CI, 0.10 − 0.67], p = 0.003).
With 25 patients out of 48 inclusions (52%) driven to a MTA, patients with aBTCs are ideal candidates for molecular profiling.
Clinical trial identification
Legal entity responsible for the study
Jean Charles Soria
L. Verlingue: Consultant Adaptherapy. E. Rouleau: Board meeting for AstraZeneca, Roche. V. Boige: Consulted or advised for Merck Serono, Amgen, Sanofi-Aventis, Prestizia and Bayer; honoraria from Amgen, Merck Serono, Roche, Novartis and Bayer; research funding from Merck Serono. J-C. Soria: Consultancy fees from AstraZeneca, Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.