Adding abiraterone to ADT did not increase fracture admissions, and lowered them in metastatic disease

Design

Secondary analysis of two randomised phase 3 trials with linked hospital data

Population

3,102 men in England with high-risk M0 or M1 prostate cancer in STAMPEDE

Primary outcome

5-year cumulative incidence of fracture-related hospitalisation

Effect

M1: 22% vs 30% (SDHR 0.77, 0.59 to 0.99); AAP+Enza 28% vs 38% (SDHR 0.69)

This secondary analysis linked 3,102 men in England from two STAMPEDE trials (randomised 2011 to 2016) to hospital records. Men with high-risk non-metastatic or metastatic prostate cancer received standard care (ADT) or standard care plus abiraterone with prednisolone, and in a later comparison abiraterone plus enzalutamide. Fracture-related hospitalisation was identified with a prespecified coding framework, with death as a competing risk.

In metastatic disease, 5-year fracture admission was lower with abiraterone (22% vs 30%; SDHR 0.77, 95% CI 0.59 to 0.99) and with abiraterone plus enzalutamide (28% vs 38%; SDHR 0.69, 0.54 to 0.88). In non-metastatic disease there was no significant difference.

Earlier meta-analyses raised concern that androgen receptor pathway inhibitors increase fractures, which can make clinicians hesitate over intensification in frail men. Here, randomised allocation shows no excess of fracture admissions, and the authors attribute the reduction in metastatic disease to better control of bone metastases. Fractures not needing admission were not captured, and bone-protective therapy and bone density were not recorded, so bone health assessment is still needed.

• Do not withhold abiraterone intensification because of fracture concern alone; fracture admissions did not rise.
• Continue bone health assessment and protection for all men on ADT, with or without abiraterone.
• Expect fewer fracture admissions in metastatic disease with intensified treatment, likely through better bone disease control.
• Remember that fractures managed without admission were not counted in this analysis.

Why it matters

It removes a common hesitation about intensifying treatment in older men with metastatic prostate cancer.

Don't overread it

Only hospitalised fractures were captured, and bone-protective therapy use was not accounted for.

The statistics, in plain English

A sub-distribution hazard ratio accounts for men who died before they could fracture. SDHR 0.77 means about 23% fewer fracture admissions; the interval (0.59 to 0.99) only just excludes no effect, whereas 0.69 (0.54 to 0.88) is firmer.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.