Top Line: Do men with metastatic, castration sensitive prostate cancer (mCSPC) benefit from the addition of an androgen receptor blocker to ADT and docetaxel?

The Study: Abiraterone, enzalutamide, apalutamide, and docetaxel all independently improve survival when added to ADT for men with mCSPC. It is unclear, though, if combining these agents provides any additional benefit. Docetaxel isn’t always the first consideration for men with low-volume, asymptomatic mCSPC, but it nevertheless improves survival even when incorporated early in treatment. The ARASENS trial made the interesting choice to investigate whether the addition of the androgen receptor blocker, darolutamide, to ADT and docetaxel improves survival in men with mCSPC. Over 1300 men received ADT (LHRH agonist or antagonist) and 6 cycles of 75 mg/m2 docetaxel. They were randomized to darolutamide or placebo. Most had de novo metastatic disease (87%), 78.2% had Gleason 8+ disease, 79.5% had bone metastases, and 17.5% had visceral metastases. The addition of darolutamide to ADT and docetaxel reduced the risk of death by 32.5% and improved overall survival at 4 years from 50.4% to 62.7%. The benefit was seen across subgroups. Times to castration resistance, painful skeletal events, and subsequent therapy were all prolonged with the addition of darolutamide. Toxicity was similar between arms and mainly reflected docetaxel-related toxicity with ~⅔ experiencing grade 3-4 toxicity in both arms. In other words, the favorable toxicity profile of darolutamide was consistent with that seen in the ARAMIS trial.

TBL: When considering first-line docetaxel and ADT for mCSPC, the addition of darolutamide significantly improves survival without increased toxicity. It’s unclear, though, if this combination is superior to ADT paired with other NCCN category 1 androgen receptor pathway inhibitors. | Smith, N Engl J Med 2022


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