Department of Surgical Oncology, Hangzhou Tumor Hospital, Hangzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2017 Aug;21(15):3496-3503.
Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported. The current study was, therefore, designed to systematically review and appraise current knowledge and conduct a meta-analysis on phase I, II, and III clinical trials in which ALK-inhibitors were used to treat NSCLC.
The PubMed online database was thoroughly searched. A total of 26 articles were included in a qualitative systematic review, and four of them were used to conduct the quantitative meta-analysis.
We found that ALK inhibitors significantly improved the overall survival (OS) and progress free survival (PFS) of NSCLC patients, especially of ALK or ROS1 gene fusion-positive cases. ALK inhibitors contributed to better therapeutic outcomes regarding increased one-year and two-year OS, PFS, and ORR (Odds ratio: 4.393, 95% CI: 3.302-5.845, p < 0.001). Visual disturbance was the most common side effect observed in the patients treated with crizotinib, whereas mild gastrointestinal reactions, such as diarrhea and nausea, were most frequent in the patients treated with the 2nd generation of ALK inhibitors.
ALK inhibitors are safe and effective in the treatment of NSCLC patients, especially those with positive ALK-EML4 gene fusion or rearrangement.
肺癌是癌症相关死亡的主要原因。超过 80%的肺癌病例是非小细胞肺癌（NSCLC），约 5%的 NSCLC 患者存在间变性淋巴瘤激酶（ALK）基因重排或与棘皮动物微管相关蛋白样 4（EML4）融合。ALK-EML4 基因融合阳性的 NSCLC 患者对 ALK 抑制剂高度敏感。虽然 ALK 抑制剂在 NSCLC 治疗中的疗效已得到一致报道，但仅有少数随机、大规模临床试验进行了报道。因此，本研究旨在对 ALK 抑制剂治疗 NSCLC 的 I、II 和 III 期临床试验进行系统评价和评估，并进行荟萃分析。
彻底检索 PubMed 在线数据库。共纳入 26 篇文章进行定性系统评价，其中 4 篇用于进行定量荟萃分析。
我们发现 ALK 抑制剂显著改善了 NSCLC 患者的总生存期（OS）和无进展生存期（PFS），尤其是 ALK 或 ROS1 基因融合阳性病例。ALK 抑制剂可提高一年和两年 OS、PFS 和客观缓解率（ORR），从而带来更好的治疗效果（优势比：4.393，95%置信区间：3.302-5.845，p<0.001）。接受克唑替尼治疗的患者最常见的副作用是视觉障碍，而接受第二代 ALK 抑制剂治疗的患者最常见的是轻度胃肠道反应，如腹泻和恶心。
ALK 抑制剂在治疗 NSCLC 患者，特别是 ALK-EML4 基因融合或重排阳性患者方面安全有效。
