3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.

Background

New hormonal agents (NHA) have been widely used to treat patients with metastatic and non-metastatic CRPC, with abiraterone, enzalutamide and apalutamide being FDA approved. Falls and fractures are common adverse events (AEs) observed in these patients. We conducted a meta-analysis of randomized controlled trials (RCTs) to characterize the incidence and relative risks (RRs) of falls/fractures associated with these drugs.

Methods

PubMed, Cochrane, Embase, abstracts presented at annual meeting of the ASCO and ESMO were searched for articles published from 2005 to December 2018. Eligible studies included phase II and III RCT of abiraterone, enzalutamide and apalutamide. Safety profile from selected studies was evaluated for all-grade and high-grade falls/fractures. Summary incidences and RR, with 95% confidence intervals, of all-grade and high-grade events were calculated using random-effects or fixed-effects model based on the heterogeneity of selected studies.

Results

5 RCT with adequate safety profile reporting on falls/fractures were selected and included a total of 6,695 patients. 2,500 patients received placebo/control and 4,195 patients received NHA. The incidence of all-grade falls for control arm and NHA arm was 5.0% and 10.0%, respectively. There was a significant increase in the risk of all-grade and high-grade falls with RR of 2.02 (95% CI 1.66-2.45; p < 0.0001) and 2.10 (95% CI 1.11-3.99; p = 0.0226), respectively. The incidence of all-grade fractures was 3.0% in control arm and 8.0% in NHA arm. There was a significant increase in the risk of all-grade and high-grade fractures with RR of 2.30 (95% CI 1.77-2.99; p < 0,0001) and 2.11 (95%CI 1.18-3.74; p = 0.0111), respectively.

Conclusions

NHAs are associated with higher risk of falls and fractures compared to placebo. However, it should be assessed with caution as the total observation time in the NHA arms were usually longer than with placebo. We could not investigate the mechanisms involved in falls, but we speculate that an effect in balance or fatigue/sarcopenia secondary to profound androgen deprivation may play a role. Moreover, fractures in CRPC patient population may impact quality of life and mortality.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.