Division of Medical Oncology, University of Colorado, Denver, Colorado.
Medical University of Gdańsk, Gdańsk, Poland.
J Thorac Oncol. 2019 Jul;14(7):1233-1243. doi: 10.1016/j.jtho.2019.03.007. Epub 2019 Mar 20.
At the prior data cutoff (February 9, 2017) the ALEX trial showed superior investigator-assessed progression-free survival (PFS) for alectinib versus crizotinib in untreated, anaplastic lymphoma kinase (ALK)-positive, advanced NSCLC (hazard ratio = 0.47, 95% confidence interval: 0.34-0.65, p < 0.001). The median PFS in the alectinib arm was not reached versus 11.1 months with crizotinib. Retrospective analyses suggest that the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) may influence ALK-inhibitor treatment benefit. We present updated analyses, including exploratory subgroup analysis by EML4-ALK variant, after an additional 10 months' follow-up (cutoff December 1, 2017).
Patients were randomized to receive twice-daily alectinib, 600 mg, or crizotinib, 250 mg, until disease progression, toxicity, death, or withdrawal. PFS was determined by the investigators. Baseline plasma and tissue biomarker samples were analyzed by using hybrid-capture, next-generation sequencing to determine EML4-ALK variant.
Baseline characteristics were balanced. Investigator-assessed PFS was prolonged with alectinib (stratified hazard ratio = 0.43, 95% confidence interval: 0.32-0.58). The median PFS times were 34.8 months with alectinib and 10.9 months with crizotinib. EML4-ALK fusions were detectable in 129 patient plasma samples and 124 tissue samples; variants 1, 2, and 3/ab did not affect PFS, objective response rate, or duration of response. Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue. Despite longer treatment duration (27.0 months in the case of alectinib versus 10.8 months in the case of crizotinib), the safety of alectinib compared favorably with that of crizotinib.
Alectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.
在先前的数据截止日期（2017 年 2 月 9 日），ALEX 试验显示，与克唑替尼相比，艾乐替尼在未经治疗的、间变性淋巴瘤激酶（ALK）阳性的晚期非小细胞肺癌（NSCLC）患者中具有更好的研究者评估无进展生存期（PFS）。艾乐替尼组的中位 PFS 尚未达到，而克唑替尼组为 11.1 个月。回顾性分析表明，棘皮动物微管相关蛋白样 4 基因-ALK 变体（EML4-ALK）可能影响 ALK 抑制剂治疗的获益。我们在另外 10 个月的随访后（截止日期为 2017 年 12 月 1 日），提供了更新的分析结果，包括根据 EML4-ALK 变体进行的探索性亚组分析。
患者被随机分配接受每日两次 600mg 的艾乐替尼或每日两次 250mg 的克唑替尼治疗，直到疾病进展、毒性、死亡或退出。PFS 由研究者确定。通过杂交捕获、下一代测序对基线血浆和组织生物标志物样本进行分析，以确定 EML4-ALK 变体。
基线特征平衡。艾乐替尼组的研究者评估 PFS 延长（分层风险比=0.43，95%置信区间：0.32-0.58）。艾乐替尼组的中位 PFS 时间为 34.8 个月，克唑替尼组为 10.9 个月。在 129 例患者的血浆样本和 124 例组织样本中可检测到 EML4-ALK 融合；变体 1、2 和 3/ab 对 PFS、客观缓解率或缓解持续时间没有影响。在血浆和组织中，艾乐替尼组的研究者评估 PFS 长于克唑替尼组，不论 EML4-ALK 变体 1、2 和 3a/b 如何。尽管艾乐替尼的治疗时间更长（27.0 个月，而克唑替尼为 10.8 个月），但与克唑替尼相比，艾乐替尼的安全性更好。
在未经治疗的 ALK 阳性 NSCLC 患者中，与克唑替尼相比，艾乐替尼继续显示出更好的研究者评估 PFS，与 EML4-ALK 变体无关。
Zotero 插件