Background

Darolutamide is an androgen receptor pathway inhibitor (ARPI) used in patients with prostate cancer (PC). In pivotal trials, it has demonstrated a favorable toxicity profile. There are no head-to-head comparison studies between the different ARPIs, but the efficacy of these drugs seems to be similar making the toxicity profile a key element for treatment selection.

Methods

We conducted a systematic review of all clinical trials assessing treatment with darolutamide for patients with PC using placebo as the control using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the safety of darolutamide versus placebo evaluating adverse events (AE) leading to treatment discontinuation and the rate of the AE reported as “AE of interest” in the ARAMIS trial. The comparison among darolutamide and the placebo group in terms of safety and tolerability was performed using odds ratio (OR) as meta-analytic outcome.

Results

We identified three articles comprising 2902 patients for the systematic review and meta-analysis (1652 treated with darolutamide and 1250 with placebo). Darolutamide did not increase AE leading to treatment discontinuation compared to placebo (pooled OR: 1.176, 95% CI 0.918–1.507, p = 0.633). Regarding the “AE of interest” there was no difference between darolutamide and placebo in terms of asthenia, cardiac arrhythmia, cardiac disorder, coronary artery disorder, depression mood disorder, falls, fatigue, heart failure, hot flushes, hypertension, mental-impairment disorder, rash, seizure and weight loss. The only “AE of interest” with a statistically significant difference in favor of placebo was bone fractures (pooled OR: 1.523, 95% CI 1.081–2.146).

Conclusions

In our systematic review and meta-analysis, darolutamide showed a toxicity profile comparable to placebo with the exception of bone fractures. In the absence of head-to-head comparison studies between the different ARPIs, the results of our research suggest a preferred use of darolutamide in the approved settings.

中文翻译：

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达洛鲁胺与安慰剂的安全性概况：系统评价和荟萃分析

背景

Darolutamide 是一种雄激素受体途径抑制剂 (ARPI)，用于前列腺癌 (PC) 患者。在关键试验中，它表现出良好的毒性特征。不同 ARPI 之间没有进行头对头比较研究，但这些药物的功效似乎相似，这使得毒性特征成为治疗选择的关键因素。

方法

我们使用 PubMed/Medline 和 Cochrane 图书馆数据库，对所有评估达洛鲁胺治疗 PC 患者的临床试验进行了系统评价，并使用安慰剂作为对照。我们还进行了荟萃分析，比较达洛鲁胺与安慰剂的安全性，评估导致治疗中断的不良事件 (AE) 以及 ARAMIS 试验中报告为“感兴趣的 AE”的 AE 发生率。使用比值比 (OR) 作为荟萃分析结果，对达洛鲁胺和安慰剂组的安全性和耐受性进行比较。

结果

我们确定了包含 2902 名患者的三篇文章进行系统评价和荟萃分析（其中 1652 名患者接受达洛鲁胺治疗，1250 名患者接受安慰剂治疗）。与安慰剂相比，达洛鲁胺不会增加导致治疗停止的 AE（汇总 OR：1.176，95% CI 0.918–1.507，p = 0.633）。关于“感兴趣的AE”，达洛鲁胺和安慰剂在乏力、心律失常、心脏疾病、冠状动脉疾病、抑郁情绪障碍、跌倒、疲劳、心力衰竭、潮热、高血压、精神障碍方面没有差异、皮疹、癫痫发作和体重减轻。唯一与安慰剂相比具有统计学显着差异的“感兴趣的不良事件”是骨折（汇​​总 OR：1.523，95% CI 1.081–2.146）。

结论

在我们的系统评价和荟萃分析中，除骨折外，达洛鲁胺的毒性特征与安慰剂相当。由于缺乏不同 ARPI 之间的头对头比较研究，我们的研究结果表明在批准的环境中优选使用达洛鲁胺。