Utilization patterns of second-generation androgen receptor pathway inhibitors as first-line therapy for prostate cancer in the United States.

BACKGROUND: Second-generation androgen receptor pathway inhibitors (ARPIs) have transformed treatment for patients with advanced prostate cancer. Despite overlapping indications and comparable efficacy among these ARPIs, their staggered market entry and differing toxicity profiles may influence real-world prescribing. We characterized temporal trends and utilization patterns of these agents as frontline treatment for advanced prostate cancer in the United States. METHODS: Using the Merative MarketScan database, we identified patients with prostate cancer receiving enzalutamide, apalutamide, or darolutamide between 2012 and 2023. ARPI therapy was classified as first-line if initiated after ≥180 days of continuous enrollment. Annual proportions of first-line initiation and overall utilization of ARPIs were assessed descriptively. Comparisons by geographic status, urbanicity, insurance plan, and metastatic status were evaluated using chi-squared testing and multivariable modeling. RESULTS: Among 1.1 million individuals with prostate cancer, 3773 patients received ARPI therapy, of whom 1914 met criteria for first-line analysis. Use of first-line darolutamide steadily increased, rising to 42% in 2023 and surpassing enzalutamide. First-line ARPI selection did not differ significantly by region, urbanicity, insurance, or metastatic status. Overall ARPI utilization increased 21-fold over the study period, with enzalutamide remaining the most common agent. In 2023, a higher proportion of darolutamide fills occurred in metropolitan areas (p = 0.0008), and among metastatic patients (p = 0.0058). CONCLUSION: Darolutamide rapidly emerged as the most selected first-line ARPI by 2023, without consistently observed differences by patient demographics. However, continued dominance of enzalutamide for overall fills may highlight durability of legacy therapy, particularly among non-metropolitan and non-metastatic populations.