Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.
Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.
复制标题
DOI：
10.18632/oncotarget.12897
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Huang L;Wei Y;Shen S;Shi Q;Bai J;Li J;Qin S;Yu H;Chen F
据报道，阿帕替尼可显着改善既往二线化疗失败的晚期胃癌患者的总生存期（OS）。然而，目前尚不清楚阿帕替尼是否通过改善进展或延长进展后生存来发挥作用。在这里，基于III期临床试验数据，通过无进展生存期（PFS）、进展后生存期（PPS）和疾病控制率（DCR）系统地量化了阿帕替尼对患者总生存期的中介作用。 PFS 是阿帕替尼治疗与 OS 之间关联的主要中介因素，间接效应平均生存时间比为 1.63 (95%CI 1.35-1.97)，介导了 93.5% 的治疗效果。 DCR 也是次要疗效终点之间的重要中介因素，其间接效应平均生存时间比为 1.47（95% CI 1.20-1.79，50.9% 介导）。 DCR 的主要目标和其他目标都有相似的结果。结果表明，阿帕替尼治疗延长了无进展生存期，而不是进展后生存期，进而提高了总生存期。此外，我们的研究强调了临床试验中中介分析的价值，即在传统初步分析的基础上提供额外信息。
Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.