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Lack of efficacy and drug resistance: 22 case reports In a prospective cohort study involving 40 patients with metastatic prostate cancer treated with at least 1 month of androgen receptor (AR)-directed treatment between November 2018 and November 2019, 22 men aged 56–89 years were described, who developed drug resistance or exhibited lack of efficacy during treatment with abiraterone and/or enzalutamide for metastatic prostate cancer [dosages and routes not stated]. The men, who were diagnosed with metastatic prostate cancer, had been receiving abiraterone (n=7), enzalutamide (n=8) or abiraterone and enzalutamide (n=7) for at least 1 month. All patients were also maintained on standard androgen deprivation therapy. Following enrollment to the study, the patients were scheduled to undergo assessment of genomic alterations in the AR enhancer and gene body (AR/enhancer) in cell-free DNA (cfDNA), for which peripheral blood was collected. Subsequently Enhancer and Neighboring Loci of Androgen Receptor Sequencing (EnhanceAR-Seq), a targeted sequencing assay, was applied to plasma and genomic alterations were analysed with respect to matched plasma depleted whole blood and unmatched healthy donor samples. A separate blood sample was also collected for circulating tumor cell (CTC) AR-V7 analysis. Among 22 patients, 4 patients underwent serial sample collection with at least one time point, which were then applied to EnhanceAR-Seq assay. These four patients exhibited elevated AR/enhancer copy number. Based on EnhanceAR-Seq assay results, including genomic alterations in the AR/enhancer locus or AR enhancer amplification, the patients were diagnosed with primary resistance (lack of efficacy) (n=8) or secondary resistance (n=14). The AR-V7 analysis returned negative for 21 patients and positive for 1 patient. During follow-up, 13 patients exhibited disease progression, while 4 patients died, wherein 1 patient died due to metastatic castration resistant prostate cancer (mCRPC) [not all causes of death stated]. Dang HX, et al. Cell-free DNA alterations in the AR enhancer and locus predict resistance to AR-directed therapy in patients with metastatic prostate cancer. JCO Precision 803520897 Oncology 4: 680-713, Jan 2020. Available from: URL: http://doi.org/10.1200/PO.20.00047

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Reactions 12 Dec 2020 No. 1834