Department of Medical Oncology, Kinki University Faculty of Medicine, Osakasayama, Japan.
Clin Lung Cancer. 2013 May;14(3):261-6. doi: 10.1016/j.cllc.2012.09.006. Epub 2012 Oct 27.
The increased availability of active agents has improved overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). We previously showed that postprogression survival (PPS) is highly associated with OS in the first-line setting, but little is known about PPS in the salvage setting. In this study, we analyzed PPS in phase III trials in the second-line or third-line setting.
A literature search identified 18 trials for previously treated patients with advanced NSCLC. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the association between OS and either PFS or PPS. Correlation analysis to examine whether a treatment benefit for PFS carried over to OS was performed by calculation of incremental gains in OS and PFS at the trial level.
The average median PPS was longer than the average median PFS (5.4 and 2.6 months, respectively). The induction rate for subsequent chemotherapy after second-line or third-line treatment was related to the duration of PPS in linear regression analysis (r(2) = 0.4813). Median OS was highly associated with median PPS but not with PFS (r = 0.94 and 0.51, respectively), and only a weak association between the treatment benefits for PFS and OS was detected (r = 0.29).
Treatment benefit for OS in patients with advanced NSCLC can be skewed by the effects of subsequent therapies in the second-line or third-line setting. Whether PFS or OS is the more appropriate endpoint for trials in the salvage setting should be considered.
活性药物的增加提高了晚期非小细胞肺癌(NSCLC)患者的总生存期(OS)。我们之前的研究表明,二线或三线治疗后的进展后生存期(PPS)与一线治疗中的 OS 高度相关,但关于二线或三线治疗中的 PPS 知之甚少。在这项研究中,我们分析了二线或三线治疗中的 III 期试验中的 PPS。
文献检索确定了 18 项针对晚期 NSCLC 经治患者的试验。我们将 OS 分为无进展生存期(PFS)和 PPS,并评估了 OS 与 PFS 或 PPS 之间的关系。通过计算试验水平的 OS 和 PFS 的增量增益,进行了治疗对 PFS 的获益是否可以转化为 OS 的相关性分析。
平均中位 PPS 长于平均中位 PFS(分别为 5.4 和 2.6 个月)。二线或三线治疗后进行后续化疗的诱导率与 PPS 的持续时间呈线性回归分析相关(r² = 0.4813)。中位 OS 与中位 PPS 高度相关,但与 PFS 无关(r = 0.94 和 0.51),仅检测到 PFS 和 OS 之间治疗获益的弱相关性(r = 0.29)。
二线或三线治疗中后续治疗的影响可能会使晚期 NSCLC 患者的 OS 治疗获益产生偏差。是否将 PFS 或 OS 作为二线或三线治疗中的试验更合适的终点,应加以考虑。