Advanced Androgen Blockage in Nonmetastatic Castration-resistant Prostate Cancer: An Indirect Comparison of Apalutamide and Enzalutamide

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have historically had few treatment options. Recently, randomized controlled trials have examined the benefit of apalutamide and enzalutamide in these patients. We sought to perform an indirect treatment comparison using a network meta-analysis approach to compare the relative efficacy and toxicity of these two agents. The primary outcome of this analysis was metastasis-free survival (MFS) while secondary outcomes were time to prostate-specific antigen progression, overall survival, and adverse events. The Bucher technique for indirect comparison was used to compare apalutamide and enzalutamide using the common placebo comparator. We found no evidence of a significant difference in MFS (hazard ratio 1.04, 95% confidence interval 0.78–1.37) between enzalutamide and apalutamide. Similarly, there were no differences for any of the secondary outcomes. While indirect comparisons cannot supplant direct comparative data, this analysis suggests that apalutamide and enzalutamide are similarly effective in delaying metastases for patients with nmCRPC. Patient summary: Historically, there have been few treatment options for prostate cancer patients receiving androgen deprivation therapy who have rising prostate-specific antigen levels without obvious recurrence of cancer. Recent randomized controlled trials demonstrated that treatment with enzalutamide and apalutamide delayed the development of metastatic cancer. This study demonstrates through an indirect comparison that both medications are likely to have similar efficacy and side-effect profiles. Recent data support the use of apalutamide and enzalutamide in nonmetastatic castration-resistant prostate cancer. This analysis demonstrates no significant differences in efficacy and toxicity between these two agents.