br The above data demonstrate that the efficacy

The above data demonstrate that the efficacy of single-agent PARP inhibitors and PD-1 checkpoint inhibitors for mCRPC patients rely on precise patient selection. The real-world benefits of next-generation sequencing on unselected patients with mCRPC are unknown. This study describes the efficacy and clinical outcomes of a heavily pretreated cohort of patients with mCRPC who are screened for bio-marker directed therapies with the FoundationOne panel for PSB 1115 tumor tissue molecular profiling [19]. Our data sup-port the clinical utility of a precision medicine approach in an important but presently small subset of men with mCRPC.
2. Methods
We performed a single institution retrospective review of 77 men with metastatic prostate cancer treated at the Duke Cancer Center who received standard-of-care tumor tissue molecular profiling between January 2010 and April 2017. All patients were treated outside of a clinical trial as part of standard medical practice. We obtained institutional review board approval to review the charts of all patients in this series to abstract the clinical outcomes following FoundationOne testing.
The primary objective of this analysis was to describe whether molecular testing led to a change in clinical man-agement, and whether there were clinical responses in men with advanced mCRPC who received tumor molecular pro-filing with FoundationOne as described by PSA response and radiographic progression-free survival as defined by RECIST 1.1 and PCWG2 criteria. Secondary objectives were to describe the specific genomic results of all patients and their clinical outcomes with matched targeted therapies. Clinical data (including pathologic and laboratory data) were recoded and secured in a password-protected, 
auditable, institutional review board-approved REDCap database.
For the patients who received molecularly matched tar-geted therapy, board-certified, fellowship-trained radiolog-ists with expertise in abdominopelvic imaging and RECIST calculations (D.M. and R.T.G.) reviewed all imaging for response and radiographic progression-free survival per RECIST 1.1 and PCWG2 criteria [20,21].
All patients ≥18 years of age with histologically con-firmed prostate adenocarcinoma who had tumor tissue (pri-mary or metastatic) sent for FoundationOne testing within our timeframe were included in the analysis. Genomic alter-ations were classified for clinical utility based on the estab-lished OncoKB framework [22] (Supplementary Table 1). AR amplification was considered noninformative as present inhibitors have activity independent of AR DNA genomic alterations. MSI and tumor mutational burden (TMB) were not included on the FoundationOne panel at the time of our clinical testing—however, mismatch repair genes such as MLH1, MSH2, MSH6, PMS2, and EPCAM were included.
Duration of therapy was defined as the time of treatment initiation until discontinuation. No formal sample size cal-culation was necessary as this was a descriptive retrospec-tive analysis.
3. Results
Between January 2010 and April 2017, a total of 77 indi-vidual patient tumor specimens were sent to FoundationOne for genomic profiling at Duke University. Of these 77 sam-ples, 18 samples (23%) were deemed insufficient for proc-essing due to low tumor content, and thus 59 samples (77%) were successfully processed and results were reviewed by the treating oncologist (Fig. 1).
Baseline characteristics of our cohort at the time of genomic profiling are listed in Table 1. Median age was 69 years; 81% of patients were Caucasian and 14% were Afri-can American. Most patients had mCRPC (85%) while 15% had localized hormone-sensitive prostate cancer (HSPC). Genomic testing using the FoundationOne plat-form occurred after a median of 3 prior lines of therapy (range 0−8). The most common therapies prior to genomic testing were enzalutamide (63%), docetaxel (58%), abira-terone (47%), and sipuleucel-T (47%).