Long-Term Efficacy of Doublets—the ARCHES 5-Year Update

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Dr Morgans presents compelling long-term data from the ARCHES trial, demonstrating sustained efficacy of enzalutamide plus ADT with 5-year follow-up. The analysis, with median follow-up exceeding 61 months, shows remarkable stability in HRs and clinically meaningful overall survival benefits. High-volume disease patients experienced a 3-year median overall survival improvement with the addition of enzalutamide to ADT, providing concrete data for patient counseling and treatment decisions.

The ARANOTE trial’s patient-reported outcome data reveal additional benefits beyond traditional efficacy end points, including prolonged time to quality-of-life deterioration and delayed pain progression. These findings are particularly relevant for patient counseling, as they demonstrate that treatment intensification improves disease control and maintains functional status and symptom control. The quality-of-life benefits were most pronounced in prostate cancer–specific domains, including urinary function, physical function, and social functioning.

Long-term follow-up data from doublet therapy trials provide crucial evidence for the durability of treatment benefits and help establish the foundation for treatment sequencing decisions. The consistency of benefits across multiple subgroups, regardless of disease volume or patient age, supports the broad applicability of doublet therapy in appropriate candidates. These data underscore the importance of early treatment intensification and provide reassurance about the long-term risk-benefit profile of modern androgen receptor pathway inhibitors.