{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Smith MR"],"funding":["NCI NIH HHS"],"pagination":["963-970"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5568792"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["70(6)"],"pubmed_abstract":["Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.To evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).We conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] ?8 ng/ml or PSA doubling time [PSA DT] ?10 mo).Patients received 240mg/d apalutamide while continuing on androgen-deprivation therapy.Primary end point was 12-wk PSA response (Prostate Cancer Working Group 2 criteria). Secondary end points included safety, time to PSA progression (TTPP), and metastasis-free survival (MFS).A total of 51 patients were enrolled; four patients with metastatic disease were excluded from the efficacy analysis. Patient characteristics included median age, 71 yr; Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score ?7 (57%); median PSA 10.7 ng/ml; and PSA DT ?10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had ?50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo-not reached [NR]); median MFS was NR (95% CI, 33.4 mo-NR). Most of the patients discontinued study treatment (n=33) due to disease progression (n=11 [22%]) or adverse events (AEs) (n=9 [18%]). The most common AE was fatigue (any grade, n=31 [61%]) although grade ?3 fatigue was uncommon (n=2 [4%]). These represent the first apalutamide nmCRPC patient clinical data.In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control.Antitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting.ClinicalTrials.gov identifier NCT01171898."],"journal":["European urology"],"pubmed_title":["Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort."],"pmcid":["PMC5568792"],"funding_grant_id":["P30 CA008748"],"pubmed_authors":["Shore ND","Bandekar R","Smith MR","Rathkopf DE","Berry WR","Chow Maneval E","de Boer CJ","Ryan CJ","Antonarakis ES","Higano CS","Alumkal JJ","Yu MK","Liu G"],"additional_accession":[]},"is_claimable":false,"name":"Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort.","description":"Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets.To evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).We conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] ?8 ng/ml or PSA doubling time [PSA DT] ?10 mo).Patients received 240mg/d apalutamide while continuing on androgen-deprivation therapy.Primary end point was 12-wk PSA response (Prostate Cancer Working Group 2 criteria). Secondary end points included safety, time to PSA progression (TTPP), and metastasis-free survival (MFS).A total of 51 patients were enrolled; four patients with metastatic disease were excluded from the efficacy analysis. Patient characteristics included median age, 71 yr; Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score ?7 (57%); median PSA 10.7 ng/ml; and PSA DT ?10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had ?50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo-not reached [NR]); median MFS was NR (95% CI, 33.4 mo-NR). Most of the patients discontinued study treatment (n=33) due to disease progression (n=11 [22%]) or adverse events (AEs) (n=9 [18%]). The most common AE was fatigue (any grade, n=31 [61%]) although grade ?3 fatigue was uncommon (n=2 [4%]). These represent the first apalutamide nmCRPC patient clinical data.In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control.Antitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting.ClinicalTrials.gov identifier NCT01171898.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Dec","modification":"2020-11-19T16:47:26Z","creation":"2019-03-27T02:54:20Z"},"accession":"S-EPMC5568792","cross_references":{"pubmed":["27160947"],"doi":["10.1016/j.eururo.2016.04.023"]}}