1785P - Changes in bone mineral density, trabecular bone score and body composition in metastatic hormone-sensitive prostate cancer (mHSPC) patients randomized to receive androgen deprivation + enzalutamide plus/minus zoledronic acid: The BonEnza study

Background

Androgen deprivation therapy (ADT) is associated with increased fracture risk, due to bone loss and bone quality impairment, as well as with profound alterations in body composition favoring the transition to sarcopenic obesity. Additional metabolic effects of next generation hormonal agents (NGHA) in combination with ADT have been poorly studied.

Methods

BonEnza (NCT03336983) is a prospective phase II trial in which mHSPC patients were randomized to receive either ADT plus enzalutamide (E arm) or the same combination with the addition of zoledronic acid (EZ arm). Bone mineral density (BMD), trabecular bone score (TBS), fat body mass (FBM) and lean body mass (LBM) were assessed at baseline and after 18 months using dual energy x-ray absorptiometry (DEXA) scan.

Results

From February 2018 to December 2022, a total of 89 patients (46 from EZ arm and 43 from E arm), had paired DEXA evaluation at both timepoints. Femoral BMD and TBS significantly reduced in E arm (-9.1%, p<0.001; -3.1%, p=0.001, respectively), while they increased in EZ arm (5.3%, p<0.001; 2.8%, p=0.008, respectively). FBM increased by 22.7% (p<0.001) and LBM decreased by 6.3% (p<0.001) after 18 months of therapy, irrespective of study arm.

Conclusions

The addition of enzalutamide to ADT is associated with a marked reduction in BMD and impaired bone quality as measured by TBS. Both effects are prevented by zoledronic acid administration. The reduction in LBM and increase in FBM were doubled compared to previous observations with ADT alone, putting patients at an elevated risk of sarcopenic obesity.

Clinical trial identification

NCT03336983.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Astellas.

Disclosure

A. Dalla Volta: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Funding: Janssen, Ipsen, Astellas. All other authors have declared no conflicts of interest.