Impact of Treatment Intensification with Abiraterone on Fracture-related Hospitalisation in Newly Diagnosed Prostate Cancer: A Secondary Analysis of Two Randomised Phase 3 Trials Within the STAMPEDE Trial Platform.

Abstract

Background: Prostate cancer (PCa) patients are at increased fracture risk due to the need for androgen deprivation therapy (ADT) and progressive bone metastases. Previous meta-analyses of randomised controlled trials suggest that androgen receptor pathway inhibitors (ARPIs) increase fracture risk.

Objective: We assessed the impact of abiraterone-based treatment intensification on fracture-related hospitalisation (FRH) within the STAMPEDE trial platform.

Design, setting and participants: We performed a secondary analysis of two STAMPEDE trials in patients with high-risk non-metastatic (M0) or metastatic (M1) disease.

Interventions: Patients were allocated to either standard of care (SOC) or SOC plus abiraterone with prednisolone (AAP) or, in a later comparison, SOC+AAP with enzalutamide (Enza).

Outcome measurements and statistical analysis: A prespecified coding framework within Hospital Episode Statistics (HES) identified FRHs. Flexible parametric competing-risk models estimated 5-year cumulative incidence of FRH and sub-distribution hazard ratios (SDHR), with death as a competing risk.

Outcome measurements and statistical analysis: Between Nov 2011 and Mar 2016, 3893 patients were randomised to the STAMPEDE AAP±Enza trials. Linked HES data were available for 3102 patients in England. In M1 disease, 5-year FRH incidence was significantly lower with SOC + AAP than SOC alone (22% vs 30%; SDHR 0.77, 95%CI 0.59-0.99; p = 0.04) and with SOC + AAP + Enza than SOC alone (28% vs 38%; SDHR 0.69, 95%CI 0.54-0.88; p = 0.002). No significant difference was observed in M0 patients. Limitations include potential under-estimation of total fracture burden by exclusion of non-hospitalised fractures, lack of baseline assessment of fracture risk including bone mineral density, and longitudinal use of bone-protective therapy.

Conclusions: Abiraterone-based treatment intensification did not increase FRH compared to SOC alone. In M1 disease, abiraterone reduced rather than augmented fracture risk, most plausibly reflecting improved metastatic bone disease control.