Interpreting ARANOTE: Darolutamide in Doublet and Triplet Therapy for Metastatic Castration-Sensitive Prostate Cancer

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Dr Shore provides expert interpretation of the ARANOTE trial data in the context of broader treatment paradigms for metastatic castration-sensitive prostate cancer. The challenge of obtaining long-term overall survival data from the ARANOTE study, given patient crossover and subsequent therapies, highlights the complexities of modern clinical trial design. Despite this limitation, the robust radiographic progression-free survival benefit and supporting data from the ARAMIS trial in nonmetastatic castration-resistant prostate cancer provide confidence in darolutamide’s efficacy profile.

The comparison between doublet and triplet approaches with darolutamide requires careful consideration of patient-specific factors, including tumor burden, performance status, and comorbidities. The “first shot, best shot” philosophy supports aggressive up-front treatment when patients are most likely to benefit and tolerate intensive therapy. However, treatment selection must be individualized based on risk tolerance, patient preferences, and clinical characteristics.

Successful implementation of evidence-based treatment approaches requires moving beyond traditional treatment paradigms toward shared decision-making models that fully inform patients about available options. The integration of molecular testing and precision medicine approaches will further complicate treatment selection but offers the potential for more effective, personalized therapy. Clinical expertise in balancing efficacy, toxicity, and quality-of-life considerations becomes increasingly important as treatment options expand and patient survival improves.