克唑替尼治疗间变性淋巴瘤激酶重排的非小细胞肺癌的疗效和安全性：系统评价和荟萃分析。

WHAT IS KNOWN AND OBJECTIVE

Ceritinib is a new, oral, potent and selective second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the Food and Drug Administration of the United States in April 2014. It is active in crizotinib-resistant patients, especially in patients with non-small cell lung cancer (NSCLC) and brain metastasis. The aim of this study was to analyse the effects and side effects of ceritinib in ALK-rearranged NSCLC.

METHODS

We searched articles published from January 1980 to March 2019 in PubMed, EMBASE, Cochrane Library and Web of Science. The pooled estimate and 95% CI were calculated with DerSimonian-Laird method and the random effect model.

RESULTS AND DISCUSSION

From 15 articles, 2,598 patients were included in the meta-analysis. Eleven studies reported the ORR, and the DCR was presented in 10 studies. The ORR and DCR of ceritinib were 0.48 (95% CI, 0.39-0.57) and 0.76 (95% CI, 0.69-0.82), respectively. The PFS and OS were presented in nine and three eligible studies, respectively. The PFS and OS of ceritinib were 7.26 months (95% CI, 5.10-9.43) and 18.73 months (95% CI; 14.59-22.87). These results suggested that ceritinib can effectively treat patients with ALK-rearranged NSCLC. Diarrhoea, nausea and vomiting were the three most common AEs and occurred in 69% (95% CI 51.7-87.1%), 66% (95% CI 47.0-85.8%) and 51% (95% CI 35.9-66.8%) of patients, respectively. Considering serious gastrointestinal AEs, antiemetic and antidiarrhoeal drugs should be considered to improve a patient's tolerance to ceritinib.

WHAT IS NEW AND CONCLUSION

Ceritinib is effective in the treatment of patients with ALK-rearranged NSCLC with crizotinib resistance. The DCR was up to 76%, and PFS was extended to 7.6 months. The AEs were acceptable.

已知和目的

塞瑞替尼是一种新型、口服、有效且选择性的第二代间变性淋巴瘤激酶（ALK）抑制剂，于 2014 年 4 月获得美国食品和药物管理局批准。它对克唑替尼耐药的患者有效，尤其是对非小细胞肺癌（NSCLC）和脑转移患者有效。本研究旨在分析塞瑞替尼在 ALK 重排的 NSCLC 中的疗效和副作用。

方法

我们在 PubMed、EMBASE、Cochrane 图书馆和 Web of Science 中检索了 1980 年 1 月至 2019 年 3 月发表的文章。采用 DerSimonian-Laird 法和随机效应模型计算汇总估计值和 95%置信区间。

结果和讨论

从 15 篇文章中，共有 2598 例患者纳入荟萃分析。11 项研究报告了客观缓解率（ORR），10 项研究报告了疾病控制率（DCR）。塞瑞替尼的 ORR 和 DCR 分别为 0.48（95%CI，0.39-0.57）和 0.76（95%CI，0.69-0.82）。9 项和 3 项合格研究分别报告了无进展生存期（PFS）和总生存期（OS）。塞瑞替尼的 PFS 和 OS 分别为 7.26 个月（95%CI，5.10-9.43）和 18.73 个月（95%CI；14.59-22.87）。这些结果表明，塞瑞替尼可有效治疗 ALK 重排的 NSCLC 患者。腹泻、恶心和呕吐是最常见的三种不良反应，发生率分别为 69%（95%CI，51.7-87.1%）、66%（95%CI，47.0-85.8%）和 51%（95%CI，35.9-66.8%）。鉴于严重的胃肠道不良反应，应考虑使用止吐药和止泻药来提高患者对塞瑞替尼的耐受性。