[Treatment of Patients with ALK-positive Non-small Cell Lung Cancer and Brain Metastases]

Zhongguo Fei Ai Za Zhi. 2016 Aug 20;19(8):519-24. doi: 10.3779/j.issn.1009-3419.2016.08.06.
[Article in Chinese]

Abstract

Background: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. The standard modality of ALK-positive NSCLC with brain metastases remains uncertain.

Methods: We collected data on clinical characteristics and treatment of patients with ALK-positive NSCLC and brain metastases between March 2013 and March 2016 and retrospectively analyzed patient outcomes.

Results: In 84 ALK-positive patients with advanced NSCLC, 22 (26.2%) had brain metastases during the initial diagnosis of lung cancer, among which 3 patients with EGFR mutation were excluded, and 19 patients were analyzed. Median intracranial progression-free survival (PFS) was 12.0 months. PFS for patients who received first-line local brain therapy (P=0.021) and crizotinib therapy (P=0.030) was superior to PFS for patients without such therapies. PFS for patients who received first-line crizotinib combined with local brain therapy was 27.0 months and only 4.2 months for those who received crizotinib alone.

Conclusions: First-line crizotinib therapy combined with local brain treatment can improve intracranial PFS for ALK-positive NSCLC with brain metastases. This finding should be confirmed further through multicenter, prospective clinical trials with large sample size.

背景与目的 间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)阳性非小细胞肺癌(non-small cell lung cancer, NSCLC)是肺癌的一个重要亚型。ALK阳性NSCLC脑转移患者的治疗尚无标准模式。方法 本研究对我院2013年3月-2016年3月期间确诊的ALK阳性NSCLC脑转移患者的临床资料和治疗情况进行回顾性分析,探讨不同治疗模式患者的转归。结果 84例晚期ALK阳性NSCLC患者中,22例初诊时有脑转移,剔除3例合并表皮生长因子受体(epidermal growth factor receptor, EGFR)双突变患者,共19例纳入分析。中位颅内疾病进展时间(progression-free survival, PFS)为12.0个月,一线脑部局部治疗(P=0.021)及一线克唑替尼治疗(P=0.030)可延长PFS;一线克唑替尼联合脑部局部治疗的中位颅内PFS为27.0个月,而单纯克唑替尼治疗的PFS仅为4.2个月。结论 一线克唑替尼联合脑部局部治疗有助于延长ALK阳性晚期NSCLC患者的颅内PFS,因例数少,尚有待大样本多中心前瞻性临床研究证实。.

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Crizotinib
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases