In STAMPEDE, abiraterone did not increase fracture hospitalisation and reduced it in metastatic disease

Design

Secondary analysis of two randomised phase 3 STAMPEDE comparisons, linked hospital records

Population

3,102 of 3,893 men with high-risk non-metastatic or metastatic prostate cancer

Primary outcome

Fracture-related hospitalisation, 5-year cumulative incidence with death as a competing risk

Effect

Metastatic: 22% vs 30%; SDHR 0.77 (95% CI 0.59 to 0.99)

This secondary analysis of two randomised STAMPEDE comparisons linked trial data to English hospital records for 3,102 of 3,893 men. They had high-risk non-metastatic or metastatic prostate cancer and received standard care with or without abiraterone and prednisolone, or with enzalutamide added.

In metastatic disease, five-year fracture-related hospitalisation was lower with abiraterone than standard care alone (22% vs 30%; subdistribution HR 0.77, 95% CI 0.59 to 0.99) and with abiraterone plus enzalutamide (28% vs 38%; 0.69, 95% CI 0.54 to 0.88). There was no significant difference in non-metastatic disease.

The authors suggest better control of bone metastases may explain the reduction. Limitations include missing non-hospitalised fractures, no baseline bone density and unrecorded use of bone-protective drugs.

• Do not withhold abiraterone for fear of fractures on this evidence alone.
• Still assess bone health in every man starting long-term hormone therapy.
• Consider bone-protective treatment according to fracture risk, which was not recorded in the trial.
• Remember that fractures not needing hospitalisation were not counted.

Why it matters

It counters a worry from earlier meta-analyses that these drugs raise fracture risk.

Don't overread it

A secondary analysis of trial data with fractures counted only if hospitalised; it does not show a protective effect of abiraterone on bone.

The statistics, in plain English

A subdistribution hazard ratio of 0.77 allows for death as a competing event, which matters because men with metastatic disease often die before a fracture. The effect is on hospitalised fractures only, which is a narrower measure than all fractures.

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