Efficacy of novel androgen axis inhibitors for the treatment of hormone-sensitive prostate cancer in patients with visceral metastases: a systematic review and meta-analysis

Abstract

Background. The presence of visceral metastases (VM) is a significant adverse prognostic factor affecting the overall survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Recently, new drugs, such as novel antiandrogen therapies (NAT), have been introduced, expanding the options for the treatment of mHSPC.Aim. To assess whether presence or absence of VM at baseline affects risk of death in patients with mHSPC receiving NAT therapy in combination with androgen deprivation therapy (ADT) compared with standard therapy (ADT ± 1st generation antiandrogen).Search strategy. Bibliographic databases PubMed and Google Scholar were searched from inception through January 21, 2022.Selection criteria. Eligible studies were randomized clinical trials with parallel design in patients with mHSPC. Subgroups of patients with or without VM at baseline were required. The following drugs were chosen as interventional agents: abiraterone acetate, apalutamide, enzalutamide, darolutamide. All in addition to ADT. The main outcome was overall survival.Data analysis. We applied the inverse variance technique for the meta-analysis of hazard ratios (HR). In HR analysis we adopted a fixed-effect model.Results. The analysis included three randomized clinical trials with 3376 patients, of which a total of 485 (14.4 %) patients had VM. Compared with ADT, the risk of death in patients with VM treated with NAT + ADT (HR 0.69; 95 % confidence interval (CI) 0.53–0.89; n = 485; p = 0.004) was similar to the risk of death in patients without VM (HR 0.66; 95 % CI 0.59–0.75; n = 2461; p <0.00001). The test for subgroup differences suggests that there is no statistically significant subgroup effect (χ2 = 0,05; df = 1; p = 0,82; I2 = 0 %). Ordered from the most to the least effective, treatments with improved overall survival in patients with VM when added to ADT included abiraterone acetate (HR 0.58; 95 % CI 0.41–0.82), apalutamide (HR 0.76; 95 % CI 0.47–1.23), enzalutamide (HR 1.05; 95 % CI 0.54–2.04). In patients without VM, the drugs are in the following order: enzalutamide (HR 0.62; 95 % CI 0.47–0.82), apalutamide (HR 0.65; 95 % CI 0.52–0.81), abiraterone acetate (HR 0.69; 95 % CI 0.58–0.82).Conclusion. Patients with mHSPC benefit from the combination of NAT with ADT, regardless of the presence or absence of VM (HR 0.67; 95 % CI 0.60–0.75; n = 2946; p <0,00001). Abiraterone acetate has the greatest advantages in reducing the risk of death in patients with VM.