• Justin F Gainor, Carol A Sherman, Kathryn Willoughby, Jennifer Logan, Elizabeth Kennedy, Priscilla K Brastianos, Andrew S Chi, and Alice T Shaw.
• *Department of Medicine, Massachusetts General Hospital, Boston, MA; †Department of Medicine, Medical University of South Carolina, Charleston, SC; and ‡Department of Neurology, Massachusetts General Hospital, Boston, MA.
• J Thorac Oncol. 2015 Feb 1;10(2):232-6.

BackgroundLeptomeningeal 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.MethodsWe 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.ResultsFour 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.ConclusionsAlectinib 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.

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