Analysis of next-generation sequencing has given physicians a depth of information regarding molecular aberrations beyond the capacity of traditional DNA sequencing technologies, but it has not led to breakthroughs in treatment and is not providing treatment recommendations for many patients. There is a need for better predictive assays to match the right drug with the right patient. At the 2020 American Association for Cancer Research annual meeting, Astrid Margossian, MD, PhD, Chief Medical Officer, SEngine Precision Medicine, Seattle, WA, presented results of a new assay designed to address this.
Dr Margossian and colleagues developed a Clinical Laboratory Improvement Amendments (CLIA)-certified functional drug assay using patient-derived tumor organoids that has application for all solid tumors. The assay measures drug sensitivity and the personalization of response through the Sensory Processing Measure (SPM) score and provides an actionable report outlining targeted therapies, endocrine treatments, and chemotherapy agents as a tool for clinicians’ 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. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting.
The objectives of this study were to determine the concordance between organoid drug sensitivity measured by SPM score with genomic anchors from genomic reports, and to examine the clinical correlation with previous treatments.
A total of 19 samples from 17 patients (age, 36-73 years; mean age, 51 years) with advanced or metastatic cholangiocarcinoma (CCA) were taken for analysis. The samples included surgical specimens, core biopsies, or fluids, such as ascites or pleural effusion. The team tested organoid sensitivity using the CLIA-certified functional drug assay to each drug in a library of up to 120 approved and investigational drugs. The response was quantified with an SPM score that integrates drug sensitivity with response personalization, using scores from 1 to 100, with a higher score indicating a better response.
Of the 19 samples, 14 were successfully screened and clinical and genomic data were captured for 10 of the total 17 patients for evaluation; patients who did not have a full clinical history and genomic profiling were not included in this analysis. An average of 71 drugs were used per screening for each patient, with the test identifying the top 7 scoring drugs per test. The test reports were completed in an average time of 17 days.
The case of a 44-year-old woman with stage IIIB multifocal intrahepatic CCA was presented in the poster. The patient’s disease progressed during 5 rounds of treatment, including 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. Resistance to the previous regimens was verified via the drug assay, but the test also demonstrated sensitivities to histone deacetylase inhibitors, SRC kinase inhibitors, mTOR inhibitors, BRAF inhibitors, oxaliplatin, and the multikinase inhibitor midostaurin (Rydapt). The patient received dasatinib (Sprycel, an SRC kinase inhibitor) and reached remission for 4 months.
According to Dr Margossian and colleagues, the test indicated that 87% of the samples had good concordance with actionable genomic anchors and 100% concordance with retrospective treatments, and that 3 patients in the study had concordance with prospective treatment response.
In an interview with CCA News, Dr Margossian stated, “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.”
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