Eligible patients were randomized to either conventional treatment or to a personalize medicine approach in a 1:2 ratio. Patients randomized to the conventional arm were treated with standard of care therapy. Patients randomized to the experimental arm underwent a tumor biopsy that was used to determine Whole Exome Sequencing (WES) (NextSeq, Illumina) and to generate an Avatar model. Once the patient derived xenograft (PDX) had been established, part of this sample was used to establish a patient derived organoid (PDO) model. Treatment was based on the targets identified by genetic and bioinformatic analysis, as well as by phenotypic screening of 40 anticancer agents (High Throughput Screening, HTS) in the patient derived models.
Until January 2020, 128 of the 146 patients have been enrolled. Of the 128 patients enrolled in the study, 83 were randomized to the experimental arm and 45 to the conventional one. A WES and PDX has been obtained from 60 % and 65 % of patients respectively. All PDX models can be converted in a PDO. Patients are currently in follow up to determine outcome.
Another goal for this project was to evaluate the feasibility of identifying druggable somatic mutations on PDACs from patients’ plasma performing WES of circulating free DNA (cfDNA). Although relatively low levels of cfDNA have been observed in PDACs on different studies, yielding poor and/or inconsistent concordant results between liquid biopsy and tumour-based assays in this type of cancer, we have shown that the WES-cfDNA is feasible and enables the identification of somatic mutations of potential clinical interest in some cases with PDACs when the exome sequencing of the biopsy came as non-informative. Using this innovative technology, we identified mutations (like ROS1 and ARID1A) that were confirmed by WES performed in patients’ tumours and/or PDX. In other patients we have been able to monitor the evolution of some genes that have led to drug resistance through treatment.
