Patient-derived tumor organoids may have clinical application to predict drug responses in a personalized treatment setting; they have shown concordance with actionable genomic anchors and retrospective treatment outcomes.
Physicians now have a depth of information regarding molecular aberrations beyond the capacity of traditional DNA sequencing technologies because of analysis of next-generation sequencing. However, it has not led to treatment breakthroughs and is not providing treatment recommendations for many patients. Better predictive assays are needed to match the right drug with the right patient. At this year’s annual meeting of the American Association for Cancer Research, Astrid Margossian, MD, PhD, Chief Medical Officer, SEngine Precision Medicine, Seattle, WA, presented results of a new assay designed to address this issue.
A Clinical Laboratory Improvement Amendments (CLIA)-certified functional drug assay was developed by Dr Margossian and colleagues using patient-derived tumor organoids that can be applied for all solid tumors. The assay measures drug sensitivity and the personalization of response through the Sensory Processing Measure (SPM) score, providing an actionable report that outlines targeted therapies, endocrine treatments, and chemotherapy agents to help clinicians make therapeutic decisions.
Organoids are 3-dimensional structures derived from tumor tissue or tumor-specific stem cells that mimic tumor characteristics, including tumor-cell heterogeneity. Organoids unite many structural and functional aspects of their in vivo counterpart organs. Based on recent evidence, organoids have been shown to help predict drug responses accurately in a personalized treatment setting.
This study aimed to determine the concordance between organoid drug sensitivity measured by SPM score with genomic anchors from genomic reports. The study also aimed to examine the clinical correlation with previous treatments.
Taken for analysis were 19 samples from 17 patients aged 36 to 73 years (mean age, 51 years) with advanced or metastatic CCA. These samples included surgical, core biopsy, and fluids, such as ascites or pleural effusion. Organoid sensitivity was tested using the CLIA-certified functional drug assay to each drug in a library of <120 approved and investigational drugs. Response was quantified with an SPM score integrating drug sensitivity with response personalization using scores from 1 to 100; a higher score indicated a better response.
Fourteen of the 19 samples were screened successfully, and clinical and genomic data were captured for evaluation of 10 of the total 17 patients. Those patients who did not have a full clinical history and genomic profiling were not included in the analysis. There was an average of 71 drugs used per screening per patient, with the test identifying the top 7 scoring drugs per test. Test reports were completed in an average time of 17 days.
Presented in the poster was a case of a 44-year-old woman with stage IIIB multifocal intrahepatic CCA. Her disease progressed during 5 rounds of treatment, which included capecitabine, the FGFR inhibitor pemigatinib (Pemazyre), cisplatin plus gemcitabine, pressurized peritoneal aerosol chemotherapy with cisplatin and doxorubicin, and olaparib (Lynparza).
A paracentesis sample was obtained, and cultured organoids were developed and tested for 48 targeted drugs and chemotherapies for sensitivity. The drug assay verified the resistance to the previous regimens, but the test also showed sensitivities to histone deacetylase inhibitors, SRC kinase inhibitors, mTOR inhibitors, BRAF inhibitors, oxaliplatin, and the multikinase inhibitor midostaurin (Rydapt). Remission was reached in this patient for 4 months when she received dasatinib (Sprycel, an SRC kinase inhibitor).
According to Dr Margossian and colleagues, 87% of the samples had good concordance with actionable genomic anchors and 100% concordance with retrospective treatments based on test results. In addition, concordance with prospective treatment response was achieved by 3 patients in the study.
According to Dr Margossian in an interview with CCA News, “This is a revolutionary approach that helps the oncologist in ‘everyday’ therapeutic decisions. The strong correlation of organoid drug response to previous treatment outcomes demonstrates the predictive power of our test. This innovative technique determines organoid sensitivity or resistance to oncology treatments, with a clear benefit for patients in time and toxicity.”
Source: Margossian A, et al. Cancer Res. 2020;80(16_suppl). Abstract 818.
