Astrid Margossian, MD @SEngineMedicine discusses an ASCO 2020 poster entitled Predictive value of a CLIA-approved organoid based drug sensitivity test
Precision medicine incorporates genomic, biochemical, and clinical knowledge in order to improve the selection of cancer patients for treatment. Drug research with Ex vivo has the ability to fit the right drug to the right patient. For all solid tumors, we have established a CLIA-certified functional drug assay which provides an actionable report of organoid sensitivity to targeted, endocrine and chemotherapy agents as a tool for therapeutic decisions. Objectives: To develop the predictive power of the test in relation to well-known genomic biomarkers and to classify drug sensitivity prior treatments. Proving that functional drug testing increases genomic report actionability.
From 2016 to 2019 at SEngine Precision Medicine 240 organoids from cancer patients were subjected to functional examination. Patients with advanced primary or metastatic cancer (solid tumors) that were either naïve in treatment or ineffective in previous therapies. After collection, fresh tumor cell samples from core biopsies, surgical excisions, or fluids arrived < 48 hrs and were cultured as 3D organoids. They were assessed using an answer format with a library of up to 130 compounds. Drug sensitivity was quantified using a score which combines sensitivity and individualization of the response of each patient relative to a reference population. Established genomic actionability from MSKCC OncoKB evidence levels 1-2 was challenged for correlation against findings.
Organoids were extracted from breasts (18.7%), ovaries (18.3%), colorectals (17.9%), pancreas (6.7%), and other solid tumors (38.3%). The median age was 53 (r5-83) in patients. 68 drugs were checked on average for each patient with an average response period of 18 days (r9 -37). It listed an average of 7 drugs per patient as top scoring drugs. We found a high concordance of drug sensitivity with established genomic anchors (e.g., BRCA1 / PARP inhibitors, ERBB2 / HER2, FGFR1-2 / FGFR, KRAS, PIK3CA / PI3 K) in 75 patients with genomic data, calculated as drug sensitivity among these target groups. However, in the absence of known genomic biomarkers, some patient samples demonstrated sensitivity to the targeted agents. Most notably, prior therapy review showed > 90 per cent of retrospective concordance.
Organoid-based drug testing demonstrates good concordance with genetic data and clinical retrospective data. Furthermore, functional testing recognizes candidate therapies in patients without recognized biomarkers, and may determine the importance of currently unvalidated variants.