Shaver Amy L, Nikita Nikita, Sharma Swapnil, Keith Scott W, Zarrabi Kevin K, Kelly Wm Kevin, Lu-Yao Grace
Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancers (Basel). 2025 Aug 23;17(17):2747. doi: 10.3390/cancers17172747.
: 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. : 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. : 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). : 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.
对于转移性去势抵抗性前列腺癌（mCRPC）有多种全身治疗方法，但其安全性尚不明确。本研究旨在描述mCRPC全身治疗的随机临床试验中确定的安全性，以及安全性是否因年龄而异。
我们利用了来自行业资助的mCRPC醋酸阿比特龙（AA）2/3期试验的个体患者数据。使用了临床试验储存库Vivli。由一名研究人员独立进行筛选。通过严重不良事件（SAE）的频率和比值比评估治疗的相对效果。采用系统评价和Meta分析的首选报告项目指南。亚组分析测量年龄修正后的SAE比值比。
我们确定了14项试验，共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次不良事件（阿比特龙组为98.4%，标准治疗组为97.3%）。与阿比特龙组（64.1%）相比，接受标准治疗的患者发生更严重不良事件（3级或4级）和死亡（5级）的比例更高（71.8%）。最常见的不良事件类别是“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。与标准治疗相比，接受阿比特龙治疗的患者所有事件的比值比更低。老年受试者发生严重肌肉骨骼事件的比值比低22%（OR 0.78；95%CI 0.63，0.96）。
在这项个体患者数据Meta分析中，接受阿比特龙治疗的患者发生SAE的风险并不高于接受标准治疗的患者。随机对照试验中的患者比一般人群更年轻且更健康；因此，随机对照试验的结果可能不适用于一般人群，尤其是在随机对照试验中代表性不足的人群。有必要进一步评估与阿比特龙相关的骨折和神经肌肉毒性（NMT）作为关键结局，以深入了解与这些不良事件相关的风险因素。有必要进行一项真实世界的前瞻性研究，以检查治疗相关的总体风险和益处。
