AUA 2018: Interim Analysis of an Open Label Phase II Study of Enzalutamide and Radium-233 in Symptomatic, mCRPC

San Francisco, CA (UroToday.com) Five years ago, in a landmark trial, Radium-223 (compared to placebo) demonstrated a significant improvement in overall survival (OS) (median 14.9 months vs. 11.3 months; HR 0.70, 95%CI 0.58-0.83) among men with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases [1]. Given the plethora of treatment options that have been approved for mCRPC since the 2013 publication of the ALSYMPCA trial, there is interest in combining different therapeutic modalities with Radium-223. Neal Shore, MD presented interim results of a multi-center, open label, phase II study assessing enzalutamide and Radium-223 among men with symptomatic mCRPC.  This study enrolled 39 patients with symptomatic bone metastases and CRPC. Patients were assessed at baseline, day 1 of each of six Radium-223 treatment cycles, and 30 days post final Radium-223 treatment. The primary objective was safety and tolerability. Secondary objectives included:

  • Bone pain response via the Bone Pain Index Short Form (BPI-SF)
  • Quality of life via the Functional Assessment of Cancer Therapy-Prostate (FACT-P)
  • Disease progression
  • Palliative radiotherapy requirement
  • Analgesic advancements
  • PSA and alkaline phosphatase progression
  • Additional antineoplastic therapy
  • ECOG performance status
  • Overall survival
Among the 39 men included, the median age was 70 years (range 52-83), 79.5% were Caucasian, most men were ECOG 0 (59%), median PSA was 19.2 ng/mL (range 0-826), and 87% of men completed all six treatments with Radium-223. The majority of men (84%) started enzalutamide the same day as Radium-223; enzalutamide was previously used in 15% of patients. There were 10.3% of patients that reported serious adverse events on or after Radium-223 initiation, however none were related to the treatment; 53.8% of patients had related non-serious adverse events, most commonly fatigue, nausea, anemia/worsening of anemia, and decreased appetite. Over a mean follow-up of 277 +/- 114 days, there were no deaths and no progression requiring additional antineoplastic therapy during this treatment phase. The average BPI-SF pain severity composite improved 0.7 to 1.2 at scheduled visits with Radiuim-223 administration. Both BPI-SF interference composite and FACT-P quality of life had positive trends towards improvement, but were not statistically significant. ECOG performance status remained consistent across the treatment phase. Both PSA and alkaline phosphatase, measures of disease progression, improved over the cycles of therapy:
PSA and alkaline phosphatase measures of disease progression AUA2018

Limitations of this study include the single arm design, non-randomization, open label and a relatively small sample size. However, the initial results demonstrate short term safety and tolerability among patients receiving concomitant Radium-223 and enzalutamide for men with symptomatic mCRPC. Important metrics such as improvement in pain scores, quality of life measures and maintenance of performance status were observed. A phase III randomized, prospective double arm trial (PEACE 3) comparing enzalutamide with Radium-223 vs enzalutamide alone is currently accruing patients. 

References:
1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.

Presented by: Neal Shore, MD, FACS, Carolina Urologic Research Center, Myrtle Beach, SC
Co-Authors: Paul Schellhammer, Virginia Beach, VA, Ronald Tutrone, Towson, MD, Neil Mariados, Syracuse, NY, Stacey Harrelson, Myrtle Beach, SC

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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