کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6174953 | 1600010 | 2016 | 8 صفحه PDF | دانلود رایگان |
BackgroundApalutamide 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.ObjectiveTo evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).Design, setting, and participantsWe conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] â¥8 ng/ml or PSA doubling time [PSA DT] â¤10 mo).InterventionPatients received 240 mg/d apalutamide while continuing on androgen-deprivation therapy.Outcome measurements and statistical analysisPrimary 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).Results and limitationsA 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 â¤7 (57%); median PSA 10.7 ng/ml; and PSA DT â¤10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had â¥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 â¥3 fatigue was uncommon (n = 2 [4%]). These represent the first apalutamide nmCRPC patient clinical data.ConclusionsIn high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control.Patient summaryAntitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting.Trial registrationClinicalTrials.gov identifier NCT01171898
Journal: European Urology - Volume 70, Issue 6, December 2016, Pages 963-970