AI Insight
This retrospective study of 151 prostate cancer patients found that initiating enzalutamide treatment at lower doses (≤80 mg daily) resulted in non-inferior overall survival and potentially superior progression-free survival compared to the standard 160 mg dose. Patients receiving lower doses achieved longer median overall survival (36.3 vs 20.7 months), better PSA response rates at 12 weeks (71.4% vs 48.8%), and lived to older ages (median 82.5 vs 78.3 years). The analysis included nearly complete follow-up through end of life and adjusted for prognostic factors including bone metastasis, performance status, and disease duration.
Why it matters
This challenges the current standard dosing approach for enzalutamide and suggests that lower initial doses may benefit real-world patients who are typically older and more fragile than clinical trial participants. If confirmed in prospective studies, dose-adapted strategies could reduce treatment-related side effects while maintaining or improving efficacy, potentially expanding treatment options for vulnerable patient populations.
Understand the Science
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background: Prostate cancer enzalutamide treatment is approved at a standard dose of 160 mg daily. Concerns for real-world patients — older and more fragile than those enrolled in clinical trials — have prompted consideration of initiating treatment with lower doses, but the long-term efficacy of this approach remains unknown. We evaluate the long-term survival and longevity in patients treated with standard versus upfront low-dose enzalutamide. Methods: Retrospective analysis of 151 patients treated with enzalutamide (102 receiving 160 mg; 49 receiving [≤]80 mg) between 2014–2021 at the Centre Hospitalier Universitaire de Martinique, with complete follow-up through end of life (98.7% completeness of follow-up). Primary outcomes were overall survival (OS), progression-free survival (PFS), and longevity (attained age). Results: Doses [≤]80 mg were associated with longer median OS (36.3 vs. 20.7 months), improved restricted mean OS (difference of 0.7 years, p=0.05), and enhanced longevity (median 82.5 vs. 78.3 years, p=0.004). PSA response rate at 12 weeks was higher with lower-dose (71.4% vs. 48.8%, p=0.016). In multivariable models adjusted for prognostic factors, [≤]40 mg compared with 160 mg was non-inferior regarding OS (HR=0.61, 95% CI 0.36–1.06), superior regarding PFS (HR=0.59, 95% CI 0.35–0.99), and superior regarding longevity (HR=0.48, 95% CI 0.28–0.84). Bone metastasis, poor performance status, PSA response, time to PSA nadir, and disease duration were independent predictors of outcomes. A post-hoc analysis revealed a strong association between dose and physician-prescribing profiles, ranging from “endorse-lowest-dose” to “never-deviate-from-full-dose”. Conclusions: Lower doses of enzalutamide were non-inferior to full-dose. Dose-adapted strategies warrant further investigation.