Neuropathy, Weight Loss Among Factors Linked With Fall Risk With Apalutamide for nmCRPC

Researchers have identified several factors that may be associated with risk for falls among patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide and ongoing androgen deprivation therapy (ADT) in the phase-3 SPARTAN study. Among these factors are post-treatment neuropathy, arthralgia, and weight loss.

SPARTAN was a randomized study that assigned patients with nmCRPC to apalutamide or placebo and demonstrated that apalutamide significantly improved metastasis-free survival and overall survival. However, the study also showed that patients treated with apalutamide also experienced a higher rate of falls compared with patients receiving placebo (15.6% vs. 9.0%).

This post-hoc analysis attempted to identify clinical variables associated with subsequent fall among the 806 patients treated with apalutamide.

“The identification of reliable clinical characteristics associated with falls would allow the identification of these patients and the implementation of preventive strategies,” the researchers wrote in Prostate Cancer & Prostatic Disease.

The most prevalent comorbidities that potentially contributed to falls or instability were arthritis (41.6%), diabetes (19.7%), and hearing impairment (10.4%). Of the falls reported, about one-third of falls were grade 1. A little more than 10% of falls were grade 3 and required hospitalization. Additionally, 16% of patients reported more than one fall. Median time from randomization to first fall was 9.2 months.

Baseline characteristics linked with fall risk included older age, poor ECOG performance status, history of neuropathy, history of cerebrovascular accident or transient ischemic attack, and beta-blocker use prior to apalutamide treatment.  After multivariable analysis, age, ECOG status, history of neuropathy, and beta-blocker use were independently associated with time to fall (P<.05).

“Risk factors for fall in patients with nmCRPC receiving apalutamide identified in the present study appear to be distinct from fall risk factors identified in community-living older adults, although some may be folded into ECOG PS, and use of beta-blockers may align with the risk factor of four or more prescription medications,” the researchers wrote.

The researchers then conducted an analysis of both baseline and after-baseline covariates and found that baseline characteristics remained significantly associated with fall. In addition, neuropathy, arthralgia, and weight loss were also significantly associated with time to fall.

“As the causes and interventions to prevent falls are often multifactorial, the clinical characteristics identified in the final model may be best used for screening of patients who are at increased fall risk and for ultimate referral for a multidimensional fall assessment,” the researchers wrote. “It is important to note that the impact of all clinical characteristics identified in the final multivariable model is multiplicative; a patient with multiple risk factors would have a higher fall risk than a patient who has only one risk factor.”

Reference

Clinical Characteristics Associated With Falls in Patients With Non-Metastatic Castration-Resistant Prostate Cancer Treated With Apalutamide