Abstract CT225: A randomized trial of integrated genomics, organoids and avatar mouse models for personalized treatment of pancreatic cancer

Abstract Background: Pancreatic adenocarcinoma (PDAC) remains one of the most lethal cancers. This study aimed to compare the efficacy of a comprehensive approach to precision medicine, including genomic and bio-informatic analysis of tumor biopsies, as well as modeling of the disease in Avatar Mouse Models and Patient Derived Organoids (PDO) to conventional treatment. Method: We conducted a prospective, randomized, multicenter clinical trial in which, patients with newly diagnosed advanced PDAC were randomized to either a personalized medicine approach or to a conventional treatment in a 2:1 ratio. Patients randomized to the conventional arm were treated with standard of care therapy. Patients randomized to the experimental arm underwent a tumor biopsy to determine their genetic status through whole exome sequencing (WES) and to generate an Avatar and PDO model. Personalized treatment was based on the targets identified by genetic and bioinformatic analysis, as well as by phenotypic screening of 40 anticancer agents in the patient derived models after discussion in a molecular committee. Results: A total 129 PDAC patients with a median age of 62 years old, were enrolled and 122 were included in the analysis. Seventy-eight patients were randomized to the experimental arm and 44 to the conventional one. WES has been performed in 66 patients and in 56 of them potentially actionable pathogenic variants were detected. Experimental models were successfully generated in 28 patients and screened. However, only 4 patients were treated with selected agents. The remaining 52 patients could not be treated according to the results of the study: 73% of them because of premature clinical deterioration, 8% because of delaying in obtaining results due to technical matters and 19% because the recommended treatment was not felt to have adequate data support by the molecular committee. The median overall survival (from the date of randomization until the date of death) was 8,7 months for patients from conventional arm and 8,8 months for patients from experimental arm (not statistically different). The median overall survival (from the date of randomization until the date of death) for the four patients treated according to the results of the study was 19,5 months. Conclusions: In our study, a full personalized medicine approach did not improve the overall survival of patients with PDAC. Failure to obtain genomic data and models, lack of actionable genetic alterations and targeted agents in living models, and the rapid course of PDAC limited the implementation of precision medicine treatments. Outcome was improved in the 6% of patients in whom a personalized treatment was administered. Citation Format: Manuel Hidalgo, Francesca Sarno, Laura Medina, Roberto Pazo, Ignacio Juez, Rocío García-Carbonero, Carmen Guillén-Ponce, Jaime Feliú, Carolina Alonso, Jair Tenorio_Castano, Pablo Lapunzina. A randomized trial of integrated genomics, organoids and avatar mouse models for personalized treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT225.