Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 10, Issue 2, Pages 232-236Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0000000000000455
Keywords
ALK; Anaplastic lymphoma kinase; Leptomeningeal metastases; Alectinib
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Funding
- US National Institutes of Health [5R01CA164273, C06CA059267]
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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.
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