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Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

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1. Men treated with abiraterone, prednisolone, and androgen-deprivation therapy (ADT) (combined therapy) demonstrated a significantly increased overall survival in comparison to those treated with ADT alone.

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2. Men treated with combined therapy demonstrated a significantly increased treatment failure-free survival in comparison to those treated with ADT alone.

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Evidence Rating Level: 1 (Excellent)

Study Rundown:

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The standard of care for newly diagnosed locally advanced or metastatic prostate cancer involves long-term androgen deprivation therapy (ADT) in the form orchiectomy, gonadotropin releasing hormone (GnRH) antagonists, or GnRH agonists. Abiraterone has previously been demonstrated to improve survival in ADT relapsed prostate cancer, and so this study was performed to investigate the role of this CYP17 inhibitor in newly diagnosed locally-advanced or metastatic prostate cancer.

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The overall survival rate was observed to be significantly improved in combined therapy versus the ADT-alone group. This trend was also seen for treatment failure-free survival, as treatment-failure events were significantly fewer in the combined therapy group. Regarding adverse events, 47% of patients randomized to combined therapy experienced a grade 3-5 adverse event, while this was seen in 33% of patients randomized to ADT alone.

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This study’s greatest impact is in demonstrating a role for abiraterone in the treatment of newly diagnosed, advanced prostate cancer. That strength stems from the study’s large patient recruitment and fairly lengthy follow-up. Nonetheless, a limitation to this study can be identified in the absence of an as-treated analysis for patients treated with radiotherapy, despite the study’s reporting of the proportions of each group in which radiotherapy was planned.

In-Depth [randomized controlled trial]:

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The Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial was a multiarm, multistage, prospective, randomized, controlled trial in which 1917 patients were randomized in a 1:1 ratio to receive ADT alone (n = 957) or combined therapy (n = 960) with 1000 mg abiraterone and 5 mg prednisolone, both once daily. Eligible patients had prostate cancer that was either newly diagnosed and metastatic, node-positive, or high-risk locally advanced, or relapsing disease with high risk features. The primary outcome was overall survival, defined as the time from randomization to death from any cause. Stratification of patients was performed with attention to age, treatment center, presence of metastasis, and planned use of radiotherapy. The intermediate primary outcome was failure-free survival. The median follow-up was 40 months. There were 184 deaths in the combined therapy group as compared with 262 in the ADT group (HR, 0.63; 95% CI, 0.52-0.76; p < 0.001). There were 248 treatment failures in the combined therapy group, compared to 535 treatment failures in the ADT-alone group (HR, 0.29; 95% CI, 0.25-0.34; p < 0.001). Grade 3-5 adverse events were reported in 443 of 948 (47%) in the combination group and 315 of 960 (33%) in the ADT-alone group.

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