2. Academic Validation
  3. 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

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

  • Eur Urol. 2016 Dec;70(6):963-970. doi: 10.1016/j.eururo.2016.04.023.
Matthew R Smith 1,  Emmanuel S Antonarakis 2,  Charles J Ryan 3,  William R Berry 4,  Neal D Shore 5,  Glenn Liu 6,  Joshi J Alumkal 7,  Celestia S Higano 8,  Edna Chow Maneval 9,  Rajesh Bandekar 10,  Carla J de Boer 11,  Margaret K Yu 12,  Dana E Rathkopf 13
Affiliations

Affiliations

  • 1 Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA. Electronic address: smith.matthew@mgh.harvard.edu.
  • 2 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
  • 3 UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
  • 4 Cancer Centers of North Carolina, Raleigh, NC, USA.
  • 5 Carolina Urologic Research Center, Myrtle Beach, SC, USA.
  • 6 University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
  • 7 Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.
  • 8 University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • 9 Aragon Pharmaceuticals, San Diego, CA, USA.
  • 10 Janssen Research & Development, Spring House, PA, USA.
  • 11 Janssen Biologics, B.V., Leiden, The Netherlands.
  • 12 Janssen Research & Development, Los Angeles, CA, USA.
  • 13 Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
PMID: 27160947 DOI: 10.1016/j.eururo.2016.04.023
Abstract

Background: 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.

Objective: To evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate Cancer (nmCRPC).

Design, setting, and participants: 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).

Intervention: Patients received 240mg/d apalutamide while continuing on androgen-deprivation therapy.

Outcome measurements and statistical analysis: 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).

Results and limitations: 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.

Conclusions: In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control.

Patient summary: Antitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate Cancer support continued development in this setting.

Trial registration: ClinicalTrials.gov identifier NCT01171898.

Keywords

Antitumor activity; Apalutamide; Castration-resistant prostate cancer; Safety.

Figures
Products