1 Medical School Hamburg (MSH), Hamburg, Germany ; 2 University Hospital of Grosshadern (LMU Munich, Haematology and Oncology), Munich, Germany ; 3 Medical Oncology Unit, Mönchengladbach, Germany.
Transl Lung Cancer Res. 2016 Feb;5(1):115-9. doi: 10.3978/j.issn.2218-6751.2016.01.06.
The development of molecularly targeted therapies [tyrosine kinase inhibitors (TKIs) and monoclonal antibodies] has significantly improved outcomes for patients with advanced or metastatic non-small cell lung cancer (NSCLC) resulting in improved progression-free survival (PFS), overall survival (OS) and quality of life (QoL). In addition, targeting the immune axis (CTLA-4, PD-1/PD-L1) has also shown promising results. Major goals of almost all clinical trials based on histology and molecular markers for NSCLC patients are improvements of OS and QoL. However, in the majority of these trials only small incremental improvements in OS were seen. Food and Drug Administration (FDA) and other health authorities have recommended to consider OS to be the standard clinical benefit endpoint that should be used to establish the efficacy of a treatment for NSCLC patients, however, the question remains what is clinically meaningful and how can this outcome be measured. According to suggestions of the American Society of Clinical Oncology (ASCO) Cancer Research Committee a relative improvement in median OS of at least 20% (3-4 months) is regarded to define a clinically meaningful improvement in outcome of NSCLC patients. However, this should not diminish PFS as a valid endpoint since a PFS improvement can also result in a meaningful palliation (e.g., painful bone metastases). Other factors (e.g., QoL) may also be involved to measure and to define the clinical importance of a given trial result. Using the "Quality-adjusted Time Without Symptoms of Toxicity" (Q-TWiST) analysis method it has been demonstrated that a clinically important and meaningful difference for Q-TWiST is 10-15% of OS in a study. Trials that are designed with less ambitious goals, however, may still be of benefit to individual NSCLC patients if the trial endpoints are met. Since there is no single factor which will make a trial clinically meaningful, these recommendations, however, are not intended to set standards for regulatory approval or insurance coverage but rather to encourage patients and investigators to demand more from clinical trials.
分子靶向治疗（酪氨酸激酶抑制剂[TKI]和单克隆抗体）的发展显著改善了晚期或转移性非小细胞肺癌（NSCLC）患者的预后，提高了无进展生存期（PFS）、总生存期（OS）和生活质量（QoL）。此外，靶向免疫轴（CTLA-4、PD-1/PD-L1）也显示出了有前景的结果。基于组织学和分子标志物的 NSCLC 患者临床试验的主要目标几乎都是改善 OS 和 QoL。然而，在这些试验中，只有一小部分患者的 OS 得到了改善。美国食品和药物管理局（FDA）和其他卫生当局建议将 OS 作为标准的临床获益终点，用于确定 NSCLC 患者治疗的疗效，但问题仍然是，什么是有临床意义的，如何衡量这个结果。根据美国临床肿瘤学会（ASCO）癌症研究委员会的建议，OS 的中位数相对改善至少 20%（3-4 个月）被认为是 NSCLC 患者结局改善的有临床意义的改善。然而，这不应降低 PFS 作为一个有效的终点，因为 PFS 的改善也可能导致有意义的缓解（例如，骨转移疼痛）。其他因素（例如，QoL）也可能涉及到衡量和定义给定试验结果的临床重要性。使用“无毒性症状的质量调整生存时间”（Q-TWiST）分析方法，已经证明在研究中，OS 改善 10-15%对于 Q-TWiST 是有临床意义和有意义的差异。然而，如果试验终点得到满足，那么设计目标较低的试验对于个别 NSCLC 患者可能仍然是有益的。由于没有单一的因素可以使一个试验具有临床意义，因此这些建议不是为了为监管批准或保险覆盖设定标准，而是为了鼓励患者和研究人员从临床试验中提出更多要求。
