Examining skeletal-related events in Australian men with castration-resistant prostate cancer (CRPC)

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Supportive Measures
Prostate Cancer
Presenter Angelyn Anton
Citation Annals of Oncology (2018) 29 (suppl_9): ix67-ix73. 10.1093/annonc/mdy434
Authors A. Anton1, S. Wong2, P. Parente3, A. Azad4, J.A. Shapiro5, A. Weickhardt6, J. Torres7, F. Parnis8, J. Goh9, C. Semira1, P. Gibbs1, B. Tran1, C. Pezaro3
  • 1Systems Biology And Personalised Medicine, Walter and Eliza Hall Institute, 3052 - Melbourne/AU
  • 2Medical Oncology, Western Health, Melbourne/AU
  • 3Medical Oncology, Eastern Health, 3128 - Box Hill/AU
  • 4Medical Oncology, Monash Health, Melbourne/AU
  • 5Monash School Of Medicine, Monash University, Melbourne/AU
  • 6Medical Oncology, Olivia Newton John Cancer Wellness and Research Centre, Melbourne/AU
  • 7Medical Oncology, Goulburn Valley Health, Shepparton/AU
  • 8Medical Oncology, Adelaide Cancer Centre, Adelaide/AU
  • 9Medical Oncology, Royal Brisbane and Women’s Hospital, Brisbane/AU

Abstract

Background

Bone metastases are common in CRPC, often leading to significant morbidity from skeletal-related events (SREs). SREs include pathological fractures, spinal cord compression and symptomatic bone lesions requiring radiotherapy or surgery. Bone-modifying agents (BMAs) lead to a reduction in SREs. However, no survival benefit has been demonstrated and long-term use can lead to osteonecrosis of the jaw (ONJ). In Australia, BMA use is inconsistent and the optimal timing, schedule and duration remains unclear. Our study examined SRE rates and BMA use in men with CRPC and bone metastases.

Methods

The electronic CRPC Australian Database (ePAD) prospectively collects real world data in multiple Australian sites. Baseline characteristics, treatment and survival data are recorded by review of medical records. We used ePAD to identify men with bone metastases receiving systemic therapy. Descriptive statistics were used to examine the relationship between SREs, BMA use and toxicity.

Results

We identified 263 men with bone metastases. After a median follow up of 17.2 months from development of CRPC, SREs occurred in 80 men. Over half (n = 42) developed SREs prior to initiation of systemic therapy for CRPC. Initial SREs were most often symptomatic bone lesions requiring intervention (69%). Clinically significant fractures and cord compression occurred in 17 (21%) and 6 (8%) men respectively. Of men who experienced SREs, 16 were receiving BMAs and 29 subsequently commenced BMAs. In total, 125 men (48%) received BMAs, of which over two thirds (n = 87) received denosumab. BMA use was associated with younger age (p = 0.009) but not performance status or PSA kinetics. Patients treated at sites with low BMA use (< 50% of eligible patients) had higher SRE rates (37% vs 22%, p = 0.01). BMA-related toxicity was reported in 4 patients (3%), with 1 case of documented ONJ.

Conclusions

In our ePAD analysis SREs often occurred early in the disease trajectory, prior to initiation of systemic therapy. Few patients were receiving BMAs at time of first SRE. The low ONJ rate likely reflects the limitations of retrospective data collection and a modest follow up period. The higher rate of SREs at sites with lower BMA use supports the importance of considering SRE prevention in men with CRPC.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Walter and Eliza Hall Institute.

Funding

Astellas, Amgen, AstraZeneca and Janssen have provided financial assistance for the development, installation and maintenance of the ePAD registry.

Disclosure

B. Tran: Research Funding Amgen. C. Pezaro: Honorarium: Novartis; Travel support: Amgen. All other authors have declared no conflicts of interest.