Safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel: expanded access in North America

Prostate. 2015 Jun;75(8):836-44. doi: 10.1002/pros.22965. Epub 2015 Feb 14.

Abstract

Background: The open-label, single-arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel.

Methods: Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected.

Results: Median age was 71 years (range 43-97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03-9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%).

Conclusion: In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial.

Trial registration: ClinicalTrials.gov NCT01606982.

Keywords: enzalutamide; expanded access program; metastatic castration-resistant prostate cancer; safety; treatment exposure.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Docetaxel
  • Drug Resistance, Neoplasm / drug effects
  • Fatigue / chemically induced
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nitriles
  • North America / epidemiology
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / epidemiology*
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide

Associated data

  • ClinicalTrials.gov/NCT01606982