Thoracic Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
Seoul National University Hospital, Seoul, Korea.
Cancer Res Treat. 2018 Jul;50(3):691-700. doi: 10.4143/crt.2017.280. Epub 2017 Jul 6.
Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.
This analysis evaluated previously treated and untreated patients in two randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and "as-treated" populations for efficacy and safety endpoints, respectively.
In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity.
These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.
克唑替尼对比化疗在既往治疗和未经治疗的间变性淋巴瘤激酶（ALK）阳性晚期非小细胞肺癌（NSCLC）患者中表现出了优越的无进展生存期（PFS）和客观缓解率（ORR）。我们报告了克唑替尼在两项全球性 III 期临床试验的亚洲亚人群中的安全性和疗效。
本分析评估了两项随机、开放标签的 III 期临床试验中既往治疗和未经治疗的患者，这些患者的 ALK 阳性晚期 NSCLC 处于二线（PROFILE 1007）和一线（PROFILE 1014）治疗环境中，接受克唑替尼对比化疗。在意向治疗人群和“实际治疗”人群中，按种族分别对疗效和安全性终点进行分析。
在既往治疗（n=157）和未经治疗（n=157）的亚洲患者中，与化疗相比，克唑替尼治疗的 PFS 具有统计学显著延长（PFS 的风险比为 0.526；95%置信区间为 0.363 至 0.762；p < 0.001 和风险比为 0.442；95%置信区间为 0.302 至 0.648；p < 0.001，分别）。在非亚洲人和总体人群中也观察到了相似的抗肿瘤活性。与化疗相比，在既往治疗和未经治疗的亚洲和非亚洲患者中，克唑替尼的 ORR 均具有统计学显著提高（p < 0.05）。克唑替尼最常见的治疗相关不良事件（任何等级）为视觉障碍、腹泻和恶心，在亚洲和非亚洲人群中的发生率相当，与既往治疗状态无关。大多数不良事件的严重程度为轻度至中度。
这些数据目前是唯一在同一研究中显示亚洲和非亚洲人群的数据，支持克唑替尼在既往治疗和未经治疗的 ALK 阳性晚期 NSCLC 亚洲患者中的疗效和安全性。
