University of Ottawa and the Ottawa Hospital, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
Crit Rev Oncol Hematol. 2020 Apr;148:102896. doi: 10.1016/j.critrevonc.2020.102896. Epub 2020 Feb 8.
Progression-free survival (PFS) hazard ratios and gain in median PFS are suggested predictors of overall survival (OS) gain (with gain defined as experimental arm minus control arm values). We assessed use of half-lives (time to progression/death of half remaining patients). We reviewed randomized trials from Journal of Clinical Oncology and New England Journal of Medicine, 01/2012-06/12/2017 (discovery series) and 01/01/2007-12/31/2011 (first validation series). If PFS or OS gains were significant, we used PFS/OS curve nonlinear regression analysis to estimate half-lives and defined "half-life gain" as experimental minus control arm half-life. With low crossover and significant PFS differences, PFS half-life gains ≥1.5 months had positive-predictive-values for OS gains ≥2 months of 79 % and 86 % and PFS half-life gains <1.5 months had negative-predictive-values for OS gains <2 months of 95 % and 75 %, in discovery and validation series, respectively. PFS half-life gains more reliably predicted OS gains than PFS hazard ratios or gains in median PFS. Findings were confirmed in a second validation series.
无进展生存期 (PFS) 风险比和中位 PFS 增长被认为是总生存期 (OS) 获益的预测指标（获益定义为实验组与对照组的差值）。我们评估了半衰期（进展/剩余一半患者死亡时间）的使用情况。我们对 2012 年 1 月至 2017 年 6 月 12 日（发现系列）和 2007 年 1 月 1 日至 2011 年 12 月 31 日（第一个验证系列）在《临床肿瘤学杂志》和《新英格兰医学杂志》上发表的随机试验进行了回顾。如果 PFS 或 OS 获益具有统计学意义，我们使用 PFS/OS 曲线非线性回归分析来估计半衰期，并将“半衰期获益”定义为实验组与对照组的半衰期之差。在低交叉和显著的 PFS 差异的情况下，PFS 半衰期获益≥1.5 个月时，对 OS 获益≥2 个月的阳性预测值为 79%和 86%，而 PFS 半衰期获益<1.5 个月时，对 OS 获益<2 个月的阴性预测值为 95%和 75%，在发现和验证系列中分别如此。与 PFS 风险比或中位 PFS 增长相比，PFS 半衰期获益更可靠地预测 OS 获益。在第二个验证系列中得到了证实。
