Alectinib salvages CNS relapses in ALK-positive lung cancer patients previously treated with crizotinib and ceritinib

J Thorac Oncol. 2015 Feb;10(2):232-6. doi: 10.1097/JTO.0000000000000455.


Background: Leptomeningeal metastases (LM) are an increasingly frequent and devastating complication of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Currently, the optimal management of LM in ALK-positive patients remains poorly understood as these patients have been routinely excluded from clinical trials.

Methods: We describe four ALK-positive patients with LM who were treated with the next-generation ALK inhibitor alectinib through single-patient, compassionate use protocols at two institutions. All patients had previously been treated with both FDA-approved ALK inhibitors--crizotinib and ceritinib. Patients received alectinib at a starting dose of 600 mg twice daily.

Results: Four ALK-positive NSCLC patients with symptomatic leptomeningeal disease were identified. Three of four patients experienced significant clinical and radiographic improvements in LM upon treatment with alectinib. A fourth patient had stable intracranial disease for 4 months before eventual systemic disease progression. Overall, alectinib was well tolerated. One patient required dose reduction due to grade 2 hyperbilirubinemia.

Conclusions: Alectinib is active in ALK-rearranged NSCLC patients with LM, including in patients previously treated with crizotinib and ceritinib. Additional prospective studies of alectinib in ALK-positive patients with LM are warranted.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Carbazoles / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Male
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / enzymology
  • Meningeal Neoplasms / secondary*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / pathology
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / biosynthesis


  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • alectinib