Liu Geoffrey, Zhang Jie, Zhou Zheng-Yi, Li Junlong, Cai Xiaopeng, Signorovitch James
a Princess Margaret Cancer Centre , Toronto , ON , Canada.
b Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
Curr Med Res Opin. 2016 Nov;32(11):1911-1918. doi: 10.1080/03007995.2016.1220934. Epub 2016 Sep 1.
Time to progression (TTP) is a surrogate marker of overall survival (OS). However, OS is also dependent on post-progression survival (PPS). This study evaluated the association between TTP and the duration of PPS among adult patients who received ceritinib (Zykadia ) for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC).
A pooled analysis was performed on 181 ASCEND-1 (phase I) and ASCEND-2 (phase II) patients who experienced disease progression while on ceritinib. TTP was assessed on its association with PPS in a Kaplan-Meier analysis and in Cox proportional hazard models, adjusted for clinical covariates.
Main outcomes measured include TTP, PPS, and OS.
Patients with TTP ≥6 months experienced significantly longer PPS compared to those with TTP <6 months (median: 9.8 vs. 6.5 months, log-rank p-value < .01). When TTP was assessed as a continuous variable, every 3 months of longer TTP was associated with a 21% lower hazard of death following progression (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.63-1.00; adjusted HR: 0.79, 95% CI: 0.64-0.99). This positive association translated into an OS benefit: each 3 months of longer TTP was associated with a lower hazard of death (adjusted HR: 0.46, 95% CI: 0.37-0.58). Median OS was 20.0 months for patients with TTP ≥6 months and was 10.9 months for patients with TTP <6 months.
A longer duration of TTP after treatment with ceritinib was significantly associated with a longer duration of both PPS and OS.
疾病进展时间（TTP）是总生存期（OS）的替代指标。然而，OS还取决于进展后生存期（PPS）。本研究评估了接受色瑞替尼（赞可达 ）治疗的晚期间变性淋巴瘤激酶阳性（ALK+）非小细胞肺癌（NSCLC）成年患者中TTP与PPS持续时间之间的关联。
对181例在接受色瑞替尼治疗期间出现疾病进展的ASCEND-1（I期）和ASCEND-2（II期）患者进行了汇总分析。在Kaplan-Meier分析和经临床协变量调整的Cox比例风险模型中评估TTP与PPS的关联。
测量的主要结局包括TTP、PPS和OS。
与TTP<6个月的患者相比，TTP≥6个月的患者PPS显著更长（中位数：9.8个月对6.5个月，对数秩p值<0.01）。当将TTP作为连续变量进行评估时，TTP每延长3个月，进展后死亡风险降低21%（风险比[HR]：0.79，95%置信区间[CI]：0.63-1.00；调整后HR：0.79，95%CI：0.64-0.99）。这种正相关转化为OS获益：TTP每延长3个月，死亡风险降低（调整后HR：0.46，95%CI：0.37-0.58）。TTP≥6个月的患者中位OS为20.0个月，TTP<6个月的患者中位OS为10.9个月。
色瑞替尼治疗后TTP持续时间更长与PPS和OS持续时间更长显著相关。
