Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Academic Article uri icon

Overview

abstract

  • Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC).Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment.Results: Forty-six patients enrolled in the AAP-naïve (n = 25) and post-AAP (n = 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months-not reached) and 3.7 months (95% CI, 2.8-5.6 months), and median time on treatment 21 months (range, 2.6-37.5) and 4.9 months (range, 1.3-23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59-93) and 64% (95% CI, 43-82) of AAP-naïve and 43% (95% CI, 22-66) and 10% (95% CI, 1-30) of post-AAP patients remained on treatment for 6+ and 12+ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain.Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer. Clin Cancer Res; 23(14); 3544-51. ©2017 AACR.

authors

  • Rathkopf, Dana
  • Antonarakis, Emmanuel S
  • Shore, Neal D
  • Tutrone, Ronald F
  • Alumkal, Joshi J
  • Ryan, Charles J
  • Saleh, Mansoor
  • Hauke, Ralph J
  • Bandekar, Rajesh
  • Maneval, Edna Chow
  • de Boer, Carla J
  • Yu, Margaret K
  • Scher, Howard

publication date

  • February 17, 2017

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant
  • Thiohydantoins

Identity

PubMed Central ID

  • PMC5543693

Scopus Document Identifier

  • 85024381480

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-16-2509

PubMed ID

  • 28213364

Additional Document Info

volume

  • 23

issue

  • 14