Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Findings of a systematic review and meta-analysis point to a significant increased risk of falls and fractures among prostate cancer patients given androgen receptor inhibitor (ARI) therapy.
The investigators emphasize, however, that falls and fractures were “still a rare adverse event” among ARI users and believe that the “substantial” improvements in overall survival associated with ARI therapy “may outweigh the risk of fall and fracture in some individuals.”
Zin Myint, from the Markey Cancer Center in Lexington, Kentucky, USA, and co-workers advise that “[o]ncologists should consider incorporating the fall-risk screening tool in older, active, patients with cancer in clinics.”
The team collated data for 11,382 prostate cancer patients, aged a median of 72 years, who participated in one of 11 clinical trials before August 2019, including the TITAN, SPARTAN and ARAMIS studies.
In total, 6536 men received the ARIs enzalutamide, apalutamide or darolutamide in combination with androgen deprivation therapy, while 4846 men were given bicalutamide, abiraterone or placebo.
Falls were reported by 8.0% of the ARI patients and 5.0% of the controls, with grade 3 or more severe falls occurring in 1.0% and 0.6%, respectively. Fractures were reported in a corresponding 4.0% and 2.0% of the groups, with grade 3 and more severe fractures in 1.0% and 0.5%.
The incidence of all-grade falls and fractures varied by ARI used, with apalutamide having the highest rates of both events, followed by enzalutamide and darolutamide, the researchers note.
Pooled analysis indicated that receipt of an ARI was associated with a significantly increased risk of both all-grade and grade 3 and more severe falls (relative risk [RR]=1.80 and 1.60, respectively), as well as a significant increase in the risk of all-grade and grade 3 and more severe fractures (RR=1.59 and 1.71, respectively).
Zin Myint and co-authors write in JAMA Network Open that it is “unclear” why ARI use is associated with an increased risk of falls but note that this may be linked to the ability of enzalutamide and apalutamide to cross the blood–brain barrier.
“Another possible explanation is that the sarcopenia associated with ARIs has a higher risk for fall”, they suggest.
As not all studies in the meta-analysis gave information on use of denosumab and other anti-osteoporosis drugs, the team was unable to “make a strong conclusion on whether using bone-health agents would reduce the rate of fracture.”
Nevertheless, the investigators recommend that “[a]ppropriate use of bone-targeted agents should be considered in those patients as per established guidelines.”
Zin Myint et al conclude: “Further prospective studies are warranted to identify potential mechanisms and to develop strategies that include a fall risk assessment tool to examine the risk factors for falls or fracture.”
Myint ZW, Momo HD, Otto DE, et al. Evaluation of fall and fracture risk among men with prostate cancer treated with androgen receptor inhibitors. A systematic review and meta-analysis. JAMA Netw Open 2020;3(11):e2025826. doi:10.1001/jamanetworkopen.2020.25826.
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