Next-generation sequencing complemented with mini patient-derived xenografts to guide individualized treatment for patients with aggressive-variant prostate cancer.

e17050 Background: In this prospective, open, single-center interventional study (ClinicalTrials.gov Identifier: NCT03786848), we aimed to measure the clinical utility of an functional precision medicine(FPM) , which combines genomic profiling with MiniPDX assay of patient-derived tumor cells, to identify suitable therapeutic options for patients with refractory AVPC who exceeded all standard therapy in real-time to the molecular tumor board (MTB) within a clinically actionable time-frame (<3 weeks). Methods: The primary objective was to evaluate the efficacy of such a customized combinational therapy using overall response rate (ORR). Secondary end point was growth modulation index (GMI), overall survival (OS), adverse drug reaction (ADR), clinical consistency and subgroup analysis (performance status, age, metasites, number of prior therapies, therapeutic level of evidence) for the patients receiving FPM-guided treatment. Results: There was 19 patients totally enrolled in our study. 6 patients (31.6%)were not evaluated according to study protocol and formed the natural control group, leaving 13 patients (68.4%) served as an observational cohort, and considered as 16 observational objects due to accepting two individualized treatment in our study. The initially presupposed objective was reached with patient-specific treatment options available in <21 days for 13/16 patients (81.25%, 95% CI: 0.6–1.03). Further, 62.5% (10) of the original treatment schemes provided purely by NGS date were obtained positive verification in the miniPDX models. The objective response rate (ORR) was 50% for all patients ( p < 0.01). Furthermore, nine of 16 patients (56.25%) from the primary analysis set reached a GMI (PFS on assay-guided therapy compared with PFS on prior therapy) ≥1.3 with a median GMI of 1.34 (interquartile range (IQR), 0.70–1.5).Unfortunately, the PFS on assay-guided treatment was not found a significantly increase ( P = 0.49; HR=0.82, 95% CI: 0.39 - 1.74). In addition, we found a new and effective treatment for AVPC patients with actionable genetic alterations (CDK12 mutation, PTEN-loss mutation, TP53mutation, the coexistence of TP53 mutation and PTEN-loss, BRAF-V600E mutation, and MDM2amplification). Conclusions: This is the first precision medicine trial integrated NGS date and mini-PDX models to instruct therapies in oncology. It illustrates that for patients with AVPC who exceeded all standard therapy lines, customized combinational therapy guided by FPM approach can have a significant value in clinical therapy guidance. Clinical trial information: NCT03786848 .