Division of Medical Oncology, National Cancer Centre Singapore, Republic of Singapore.
Central Hospital of Porto, University of Porto, Porto, Portugal.
J Thorac Oncol. 2016 Sep;11(9):1550-7. doi: 10.1016/j.jtho.2016.05.029. Epub 2016 Jun 8.
Crizotinib and ceritinib have been developed to treat advanced or metastatic NSCLC by inhibiting anaplastic lymphoma receptor tyrosine kinase gene (ALK). No randomized trial has compared these treatments head-to-head. We compared efficacy outcomes between patients receiving ceritinib and an external control group receiving crizotinib, both as initial ALK-targeted therapies for previously treated advanced or metastatic ALK-positive NSCLC.
Individual patient data for the ceritinib-treated patients were drawn from two single-arm trials (ASCEND-1 and ASCEND-3); published summary data for the crizotinib-treated patients were extracted from three trials (PROFILE 1001, PROFILE 1005, and PROFILE 1007). To adjust for cross-trial differences, average baseline characteristics were matched using propensity score weighting. Overall survival (OS), progression-free survival (PFS), and overall response rate were then compared between treatment groups.
Before matching, the ceritinib-treated patients (n = 189) were significantly different from the crizotinib-treated patients (n = 557) in the distribution of race and number of prior regimens. After matching, all available baseline characteristics were balanced. Compared with crizotinib, ceritinib was associated with longer OS (hazard ratio = 0.59, 95% confidence interval: 0.46-0.75) and longer PFS (median 13.8 versus 8.3 months, hazard ratio = 0.52, 95% confidence interval: 0.44-0.62) in Cox proportional hazards models. The 12-month OS was 82.6% with ceritinib and 66.0% with crizotinib in a Kaplan-Meier analysis (log-rank p < 0.001). There was no significant difference in overall response rate between ceritinib and crizotinib.
In an adjusted comparison across separate clinical trials, ceritinib was associated with prolonged OS and PFS compared with crizotinib when used as initial ALK-targeted therapy for previously treated ALK-positive NSCLC.
克唑替尼和塞瑞替尼的研发目的是通过抑制间变性淋巴瘤激酶基因（ALK）来治疗晚期或转移性 NSCLC。目前尚无头对头比较这两种治疗方法的随机试验。我们比较了接受塞瑞替尼和接受克唑替尼（均作为先前治疗的晚期或转移性 ALK 阳性 NSCLC 的初始 ALK 靶向治疗）的患者的疗效。
来自两项单臂试验（ASCEND-1 和 ASCEND-3）的个体患者数据被纳入塞瑞替尼治疗患者；从三项试验（PROFILE 1001、PROFILE 1005 和 PROFILE 1007）中提取接受克唑替尼治疗的患者的已发表汇总数据。为了调整试验间差异，使用倾向评分加权法对平均基线特征进行匹配。然后比较治疗组之间的总生存期（OS）、无进展生存期（PFS）和总缓解率。
在匹配之前，塞瑞替尼治疗患者（n=189）与克唑替尼治疗患者（n=557）在种族分布和先前治疗方案数量方面存在显著差异。匹配后，所有可用的基线特征均平衡。与克唑替尼相比，塞瑞替尼与更长的 OS（风险比=0.59，95%置信区间：0.46-0.75）和更长的 PFS（中位 13.8 个月对 8.3 个月，风险比=0.52，95%置信区间：0.44-0.62）相关，在 Cox 比例风险模型中。Kaplan-Meier 分析显示，塞瑞替尼的 12 个月 OS 为 82.6%，克唑替尼为 66.0%（对数秩检验 p<0.001）。塞瑞替尼与克唑替尼的总缓解率无显著差异。
在单独临床试验的调整比较中，塞瑞替尼作为先前治疗的 ALK 阳性 NSCLC 的初始 ALK 靶向治疗药物，与克唑替尼相比，可延长 OS 和 PFS。
