Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3
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DOI：
10.1200/jco.2015.64.2702
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发表时间：
2016-04-20
影响因子：
45.3
通讯作者：
Armstrong, Andrew J.
中科院分区：
文献类型：
--
作者：
Scher, Howard I.;Morris, Michael J.;Armstrong, Andrew J.
不断发展的治疗方法、疾病表型和生物学，以及不断变化的药物开发环境，已经创建了需要修改去势抵抗性前列腺癌（CRPC）临床试验的建议，以取代那些从以前的前列腺癌临床试验工作组。（前列腺癌临床试验工作组3 [PCWG 3]）于2012年重新召集和扩大并召开会议-2015年，根据前列腺癌临床试验工作组2的新试验数据和验证研究制定更新的标准结果PCWG 3建议基线患者评估包括肿瘤组织学、既往系统治疗和反应的详细记录以及基于转移性扩散解剖模式的疾病亚型的详细报告。试验结局指标的新建议包括症状性骨骼事件的事件终点时间，以及非转移性CRPC状态试验的首次转移时间和进展时间。PCWG 3引入了不再具有临床获益的概念，以强调疾病进展的首次证据与终止或改变治疗的临床需求之间的区别，以及记录现有病变进展与新病变发展的重要性。使用来自活组织检查的肿瘤样本的系列生物学分析，基于血液的诊断，和/结论PCWG 3通过关注最有可能影响非转移性和转移性肿瘤治疗预后的疾病表现，使药物开发更接近临床实践中未满足的需求。CRPC人群。如果试验旨在寻求药物批准的支持，建议咨询监管机构。(C)2016年美国临床肿瘤学会
PurposeEvolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.MethodsAn international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.ResultsPCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.ConclusionPCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval. (C) 2016 by American Society of Clinical Oncology