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.

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.

Author information:
Smith MR1, Antonarakis ES2, Ryan CJ3, Berry WR4, Shore ND5, Liu G6, Alumkal JJ7, Higano CS8, Chow Maneval E9, Bandekar R10, de Boer CJ11, Yu MK12, Rathkopf DE13.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier NCT01171898.

Eur Urol. 2016 Dec;70(6):963-970. doi: 10.1016/j.eururo.2016.04.023. Epub 2016 May 6.

KEYWORDS:
Antitumor activity; Apalutamide; Castration-resistant prostate cancer; Safety

Pubmed: https://www.ncbi.nlm.nih.gov/pubmed/27160947