Loic Verlingue1, David Malka2, Adrien Allorant3, Christophe Massard1, Charles Ferté4, Ludovic Lacroix5, Etienne Rouleau5, Nathalie Auger6, Maud Ngo1, Claudio Nicotra1, Thierry De Baere7, Lambros Tselikas7, Bakar Ba7, Stefan Michiels3, Jean-Yves Scoazec5, Valérie Boige2, Michel Ducreux2, Jean-Charles Soria8, Antoine Hollebecque9. 1. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. 2. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 3. Biostatistics and Epidemiology Unit, Gustave Roussy, Paris-Saclay University, CESP, INSERM, Medicine University Paris-Sud, Villejuif, France. 4. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France. 5. Laboratory of Translational Research and Biological Resource Center, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy, France; Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France. 6. Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France. 7. Department of Radiology, Gustave Roussy, Villejuif, France. 8. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; U981 INSERM, Laboratory for Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France. 9. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: antoine.hollebecque@gustaveroussy.fr.
Abstract
BACKGROUND: Recommended treatments of patients with advanced biliary tract cancer (aBTC) are limited to one chemotherapy doublet. Nevertheless, efficacy of treatment personalisation for aBTCs is supported by accumulating evidences but remains to be evaluated. PATIENTS AND METHODS: Patients with aBTCs included in the prospective clinical trial MOSCATO-01 were treated by at least one previous systemic treatment, had an ECOG performance status of 0-1, and at least one tumour site accessible to biopsy. Multiple high-throughput molecular analysis was performed on biopsies to drive the administration of molecular targeted agents (MTAs). RESULTS: From November 2011 to March 2016, 43 patients (4%) of the 1035 adult patients included in MOSCATO-01 had aBTCs with a majority of intrahepatic localisation (67%). Successful biopsy procedures and DNA extractions led to molecular portraits for 34 patients (79%). Orientation to an appropriate early clinical trial or accessible MTA(s) was possible for 23 of these patients (68%), and 18 (53%) have received matched MTA(s). Among them, the overall response rate was 33% and the disease control rate was 88%. A PFS ≥6 months was observed in 37% and the PFS ratio was >1.3 for 50% of the patients. These patients had a lower risk for death as compared to the 20 patients not orientated to a matched MTA (HR, 0.29; 95% CI, 0.11-0.76; p = 0.008). CONCLUSIONS: Within the MOSCATO-01 trial, patients with aBTCs had the highest rate of orientation to matched MTAs and derived a clear clinical benefit. A broader evaluation of these findings may improve future treatments strategies for aBTCs. TRIAL REGISTRATION: NCT01566019.
BACKGROUND: Recommended treatments of patients with advanced biliary tract cancer (aBTC) are limited to one chemotherapy doublet. Nevertheless, efficacy of treatment personalisation for aBTCs is supported by accumulating evidences but remains to be evaluated. PATIENTS AND METHODS: Patients with aBTCs included in the prospective clinical trial MOSCATO-01 were treated by at least one previous systemic treatment, had an ECOG performance status of 0-1, and at least one tumour site accessible to biopsy. Multiple high-throughput molecular analysis was performed on biopsies to drive the administration of molecular targeted agents (MTAs). RESULTS: From November 2011 to March 2016, 43 patients (4%) of the 1035 adult patients included in MOSCATO-01 had aBTCs with a majority of intrahepatic localisation (67%). Successful biopsy procedures and DNA extractions led to molecular portraits for 34 patients (79%). Orientation to an appropriate early clinical trial or accessible MTA(s) was possible for 23 of these patients (68%), and 18 (53%) have received matched MTA(s). Among them, the overall response rate was 33% and the disease control rate was 88%. A PFS ≥6 months was observed in 37% and the PFS ratio was >1.3 for 50% of the patients. These patients had a lower risk for death as compared to the 20 patients not orientated to a matched MTA (HR, 0.29; 95% CI, 0.11-0.76; p = 0.008). CONCLUSIONS: Within the MOSCATO-01 trial, patients with aBTCs had the highest rate of orientation to matched MTAs and derived a clear clinical benefit. A broader evaluation of these findings may improve future treatments strategies for aBTCs. TRIAL REGISTRATION: NCT01566019.
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