David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
Lung Cancer. 2012 Sep;77(3):475-81. doi: 10.1016/j.lungcan.2012.06.007. Epub 2012 Jul 12.
Relative to best supportive care alone, cytotoxic chemotherapy has an established role in prolonging overall survival (OS) in patients with or without previous treatment for metastatic non-small cell lung cancer (NSCLC). OS has been the principal endpoint influencing regulatory decisions regarding targeted therapies for metastatic NSCLC, including the vascular endothelial growth factor monoclonal antibody bevacizumab in the frontline setting and the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib in patients after prior treatment. Progression-free survival (PFS), another common endpoint in oncology clinical trials, has been discussed as a potential surrogate for OS in metastatic NSCLC. A number of phase III clinical trials of investigational targeted agents for treatment of metastatic NSCLC are ongoing, with OS designated as the primary endpoint in some cases and PFS in others. Both endpoints have been developed largely to evaluate outcomes in unselected populations in which a fraction of patients are anticipated to derive significant benefit. New approaches are being considered for the evaluation of targeted agents. Recent high profile trials have been designed to assess PFS using a randomized discontinuation design and disease control rate after 8 weeks of treatment. With a series of recent advances toward increasingly personalized biomarker-directed anticancer therapies, the appropriateness of the traditional regulatory approach has been questioned.
与单纯最佳支持治疗相比，细胞毒化疗在有或无转移性非小细胞肺癌（NSCLC）既往治疗的患者中已确立了延长总生存期（OS）的作用。OS 一直是影响转移性 NSCLC 靶向治疗监管决策的主要终点，包括血管内皮生长因子单克隆抗体贝伐珠单抗在一线治疗中的应用以及表皮生长因子受体酪氨酸激酶抑制剂吉非替尼和厄洛替尼在既往治疗后的应用。无进展生存期（PFS）是肿瘤学临床试验中的另一个常见终点，已被讨论作为转移性 NSCLC 中 OS 的潜在替代指标。目前正在进行多项针对转移性 NSCLC 的试验性靶向药物的 III 期临床试验，在某些情况下 OS 被指定为主要终点，而在其他情况下 PFS 则被指定为主要终点。这两个终点主要是为了评估预期有部分患者会获得显著获益的未选择人群的结果而开发的。目前正在考虑新的方法来评估靶向药物。最近的一些备受瞩目的试验旨在使用随机停药设计和治疗 8 周后的疾病控制率来评估 PFS。随着一系列针对日益个体化生物标志物导向的抗癌治疗方法的最新进展，传统监管方法的适宜性受到了质疑。
