Androgen Receptor Pathway Inhibitor Monotherapy in Prostate Cancer: Safety, Oncologic Outcomes, and Quality of Life-A Systematic Review and Meta-analysis.

Background and objective: Androgen receptor pathway inhibitors (ARPIs) as monotherapy are studied increasingly across prostate cancer disease states. We aimed to evaluate the safety, oncologic efficacy, and quality of life (QoL) of ARPI monotherapy as compared with ARPI + androgen deprivation therapy (ADT) and ADT alone.

Methods: PubMed/Medline, Embase, and Cochrane/Central were queried through June 2024 for clinical trials. The primary outcomes were the rates of adverse events (AEs) presented as risk ratios (RRs); the secondary outcomes included efficacy and QoL.

Key findings and limitations: We synthesized data from 2015 men, retrieved from 17 studies. The incidence of any AEs was similar between patients on ARPIs, ARPI + ADT (RR: 1.01, 95% confidence interval [CI]: 1-1.02, p = 0.08), and ADT (RR: 1.01, 95% CI: 0.98-1.04, p = 0.3). The incidence of grade ≥3 AEs was higher in patients on ARPI monotherapy than in those on ADT (RR: 1.18, 95% CI: 1.11-1.24, p < 0.01), driven mainly by fatigue and cardiovascular toxicity. There was no statistically significant difference in grade ≥3 AEs between patients treated with ARPIs and ARPI + ADT (RR: 1.07, 95% CI: 0.87-1.3, p = 0.4). ARPI monotherapy led to a lower incidence of hot flushes (RR: 0.4, 95% CI: 0.18-0.89, p = 0.03) but higher incidences of breast pain (RR: 6.03, 95% CI: 3.34-10.88, p < 0.01) and gynecomastia (RR: 5.73, 95% CI: 3.79-8.66, p < 0.01) than treatment with ARPI + ADT. ARPIs demonstrated promising oncologic efficacy for patients with biochemical recurrence, while maintaining favorable overall and sexual QoL.

Conclusions and clinical implications: ARPI monotherapy results in overall similar toxicities for ARPI + ADT and ADT alone. The specific AE pattern of each combination can serve as a basis to tailor therapy to each patient's needs and wishes.