Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer

• DOI: 10.1016/j.xcrm.2023.101335
• Publication Date: 2023-12-19T15:45:56Z
• Authors: Tao Tan; Dmitri Mouradov; Margaret Lee; Grace Gard; Yumiko Hirokawa; Shan Li; Cong Lin; Fuqiang Li; Huijuan Luo; Kui Wu; Michelle Palmieri; Evelyn Leong; Jordan Clarke; Anuratha Sakthian...; Helen Brasier; Jeanne Tie; Niall C. Tebbutt; Azim Jalali; Rachel Wong; Antony W. Burgess; Peter Gibbs; Oliver M. Sieber
• Keywords: Colonic Neoplasms; Australia; Humans; Antineoplastic Agents; Prospective Studies; Colorectal Neoplasms; Article

Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC.