Department of Urology, Kimmel Cancer Center, Thomas Jefferson University Philadelphia, PA.
Department of Medicine, Section of Hematology and Medical Oncology and Urology Tulane University Health Sciences Center in New Orleans, LA.
Urol Oncol. 2014 Jan;32(1):28.e1-9. doi: 10.1016/j.urolonc.2012.10.001. Epub 2013 Feb 20.
The identification of appropriate surrogate endpoints for evaluating cancer therapeutics has been of ongoing interest across various tumor types. Metastatic castrate-resistant prostate cancer (mCRPC) has been a particularly challenging area. As more targeted and novel therapies are being developed in this disease space, an urgent need exists to identify surrogate endpoints in mCRPC. The ability to discern patient benefit in the absence of patient death or other complications would facilitate both drug development and more appropriate patient care.
We reviewed the available literature and guidelines used in the development and approval of recent agents for mCRPC.
The majority of regulatory approvals of new medications have relied on overall survival (OS) or prevention of complications such as skeletal related events (SRE's). Progression-free survival measures, such as bone scans, computed tomography scans, and prostate-specific antigen related changes, have not been validated nor uniformly accepted as outcome surrogates. All of the successful recent pivotal Phase III trials designed to achieve regulatory approval in mCRPC have used either OS or SRE's as the primary endpoint.
There are significant problematic issues that exist associated with defining and implementing surrogate markers in mCRPC beyond survival and complications. Suggestions are made as to how the current situation might be improved.
在各种肿瘤类型中，寻找合适的替代终点来评估癌症疗法一直是人们持续关注的问题。转移性去势抵抗性前列腺癌（mCRPC）是一个特别具有挑战性的领域。随着该疾病领域更多靶向和新型疗法的开发，迫切需要确定 mCRPC 的替代终点。在没有患者死亡或其他并发症的情况下，能够辨别患者的获益将有助于药物的开发和更恰当的患者护理。
我们回顾了用于 mCRPC 的新药物开发和批准的现有文献和指南。
大多数新药物的监管批准都依赖于总生存期（OS）或预防骨骼相关事件（SRE）等并发症。无进展生存期的测量方法，如骨扫描、计算机断层扫描和前列腺特异性抗原相关变化，尚未得到验证，也未被普遍接受为替代终点。所有旨在获得 mCRPC 监管批准的成功的近期关键性 III 期试验都将 OS 或 SRE 作为主要终点。
在 mCRPC 中，除了生存和并发症之外，定义和实施替代标志物存在着重大的问题。就如何改善当前的情况提出了建议。
