Overall Survival with Apalutamide Versus Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer.

Introduction: Survival outcomes associated with different androgen receptor pathway inhibitors (ARPIs) prescribed for the treatment of metastatic castration (hormone)-sensitive prostate cancer (mCSPC) have not been directly compared. The objective of this study was to compare overall survival (OS) by 24 months among ARPI-naïve patients with mCSPC initiating apalutamide or enzalutamide.

Methods: A retrospective, causal longitudinal inverse probability of treatment weighted analysis was conducted to compare OS between patients initiating apalutamide or enzalutamide between December 2019 and December 2023 using de-identified linked US clinical and insurance claims data. Patients were excluded if they had prior exposure to ARPIs, had evidence of castration resistance, had < 12 months of database activity prior to ARPI initiation, were diagnosed with other primary cancers, or were treated with other advanced prostate cancer (PC)-related treatment (except docetaxel). Using an intention-to-treat approach, weighted Cox proportional hazards models were used to compare OS by 24 months between patients treated with apalutamide or enzalutamide (primary analyses; exploratory analyses used all available follow-up).

Results: Overall, 1810 and 1909 ARPI-naïve patients who initiated apalutamide or enzalutamide, respectively, were included. Measured baseline characteristics between cohorts were well balanced after weighting (for both: mean age 73.0 years, ~ 60% white, ~ 23% black or African American, ~ 78% Medicare-insured, mean Quan-CCI 8.6, ~ 20% with visceral metastasis, 56.2% with de novo PC). At 24 months post index, there was a statistically significant 23% reduction in the risk of mortality among patients who initiated apalutamide compared with enzalutamide (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.62, 0.96; p = 0.019). Results remained consistent when using all available follow-up metrics (HR 0.77; 95% CI 0.64, 0.93; nominal p = 0.008).

Conclusion: In this head-to-head causal analysis among ARPI-naïve patients with mCSPC, treatment with apalutamide resulted in better survival outcomes at 24 months compared with enzalutamide. Longer follow-up studies are required to fully determine the therapeutic comparator impact of these agents.