In a systematic review and meta-analysis reported in JAMA Oncology, Nowakowska et al found that use of second-generation antiandrogens for the treatment of prostate cancer was associated with increased risk of cognitive toxicity, fatigue, and falls in patients.
Study Details
The analysis included 12 randomized trials of second-generation antiandrogens (abiraterone, apalutamide, darolutamide, or enzalutamide) comprising 13,524 patients that reported data on cognitive toxic effects, fatigue, or falls. Outcomes were compared with control groups, which did not receive second-generation antiandrogens.
Key Findings
Increased risk of cognitive toxic effects (risk ratio [RR] = 2.10, 95% confidence interval [CI] = 1.30–3.38, P = .002), fatigue (RR = 1.34, 95% CI = 1.16–1.54, P < .001), and falls (RR = 1.87, 95% CI = 1.27–2.75, P = .001) were observed among patients receiving second-generation antiandrogens vs those in the control groups. Increased age was associated with increased risk of fatigue among patients receiving second-generation antiandrogens (P < .001).
In analysis including only studies in which both groups received traditional hormone therapy, receipt of second-generation antiandrogens was associated with increased risk of cognitive toxic effects (RR = 1.77, 95% CI = 1.12–2.79, P = .01) and fatigue (RR = 1.32, 95% CI = 1.10–1.58, P = .003).
Among studies reporting grade ≥ 3 toxicities, no increased risk for grade ≥ 3 cognitive toxicity (RR = 3.15, 95% CI = 0.50–19.98, P = .22) or grade ≥ 3 fatigue (RR = 0.93, 95% CI = 0.73–1.18, P = .55) was observed among patients receiving second-generation antiandrogens. Patients receiving second-generation antiandrogens had an increased risk for grade ≥ 3 falls (RR = 1.72, 95% CI = 1.01–2.94, P = .05).
The investigators concluded, “The findings of this systematic review and meta-analysis suggest that second-generation antiandrogens s carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.”
Kevin T. Nead, MD, MPhil, of the Department of Epidemiology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Institutes of Health, National Cancer Institute, and others. For full disclosures of the study authors, visit jamanetwork.com.
