95P Organoid sensitivity for panitumumab based on primary tumor location and mutational status

Drugs targeting the epidermal growth factor receptor (EGFR), such as panitumumab and cetuximab, are standard of care for metastatic colorectal cancer (mCRC) patients with RAS/BRAF-wildtype tumors. Nevertheless, a fraction these does not respond to them. There is clinical need an effective biomarker further select EGFR inhibition. A promising predictive in vitro response testing using patient-derived organoids (PDOs). Drug screens were performed by exposing 19 PDOs from 18 (1 patient 2 PDOs) concentration range 5 days. sensitivity was measured cell viability. Growth rate (GR) inhibition metrics used drug curve fitting (area under [GRAUC], GRmax) quantify PDO sensitivity. We compared all based on RAS/BRAF mutational status sidedness. (n=6) also (n=5), which evaluated % change sum size target lesions CT scans. derived left-sided tumors more sensitive than rectum right-sided RAS/BRAF-mutant (p < 0.05, Kruskal-Wallis test), concurrent trials. observed varying sensitivities For 6 receiving panitumumab, decrease associated most (GRAUC, GRmax). previously exposed chemotherapy did show increased resistance panitumumab. confirmed less other Even within tumors, varied. These results imply that may aid guiding molecular pathology sidedness only. demonstrate suggesting can serve treatment.