Background/objectives: Multiple systemic treatments are available for metastatic castration-resistant prostate cancer (mCRPC), with unclear safety profiles. This study seeks to describe the safety determined in randomized clinical trials of a systemic treatment for mCRPC and whether safety differs by age.Methods: We utilized individual patient data from industry-funded phase 2/3 trials in mCRPC on abiraterone acetate (AA). Vivli, a clinical trial repository site, was used. One investigator independently performed screening. Relative effects of treatment were assessed with frequencies and odds of serious adverse events (SAEs). The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Subgroup analysis measured odds of SAEs as modified by age.Results: We identified 14 trials with 4296 patients. The median age of participants was 69 years. Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]). More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent adverse event category was “Musculoskeletal and Connective Tissue Disorders”. The most frequent event types included anemia, back pain, hypertension, fatigue, hypokalemia, and bone pain. The odds of all events were lower in those receiving abiraterone compared to SOC. Odds of a serious musculoskeletal event were lower in older subjects by 22% (OR 0.78; 95% CI 0.63, 0.96).Conclusions: In this IPD meta-analysis, abiraterone acetate provides no greater risk of SAE in those receiving abiraterone than those receiving SOCs. Patients in the RCTs are younger and healthier than those in the general population; consequently, the results of RCTS might not be applied to the general population, especially those under-represented in the RCTs. There is a need to further evaluate abiraterone-related fractures and neuromuscular toxicities (NMTs) as key outcomes to gain insight into risk factors related to these adverse events. A real-world prospective study is warranted to examine the overall risks and benefits associated with treatment.
背景/目的：针对转移性去势抵抗性前列腺癌（mCRPC）存在多种系统性治疗方案，但其安全性尚不明确。本研究旨在描述mCRPC系统性治疗随机临床试验中确定的安全性，并探讨安全性是否因年龄而异。 方法：我们利用来自醋酸阿比特龙（AA）治疗mCRPC的行业资助II/III期试验的个体患者数据。数据来源于临床试验存储库Vivli。由一名研究者独立进行筛选。通过严重不良事件（SAE）的发生频率和比值比评估治疗的相对效应。研究遵循系统综述和荟萃分析报告规范。亚组分析评估了年龄对SAE比值比的影响。 结果：我们共纳入14项试验，涉及4296名患者。参与者的中位年龄为69岁。几乎所有参与者都经历了至少一种不良事件（阿比特龙组98.4%，标准治疗组97.3%）。与阿比特龙组（64.1%）相比，标准治疗组发生更严重不良事件（3级或4级）和死亡事件（5级）的比例更高（71.8%）。最常见的不良事件类别为“肌肉骨骼和结缔组织疾病”。最常见的事件类型包括贫血、背痛、高血压、疲劳、低钾血症和骨痛。与标准治疗组相比，阿比特龙组所有事件的比值比均较低。在老年受试者中，严重肌肉骨骼事件的比值比降低了22%（OR 0.78；95% CI 0.63, 0.96）。 结论：在此项个体患者数据荟萃分析中，醋酸阿比特龙并未比标准治疗带来更高的SAE风险。随机对照试验中的患者比普通人群更年轻、更健康；因此，随机对照试验的结果可能不适用于普通人群，尤其是那些在试验中代表性不足的人群。有必要进一步评估阿比特龙相关的骨折和神经肌肉毒性作为关键结局指标，以深入了解与这些不良事件相关的风险因素。需要进行真实世界的前瞻性研究来全面评估治疗相关的总体风险和获益。
肿瘤(癌症)患者之家