Alectinib active against leptomeningeal metastases in ALK-positive NSCLC

By Shreeya Nanda, Senior medwireNews Reporter

Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) who have leptomeningeal metastases may benefit from treatment with the second-generation ALK inhibitor alectinib, a case series suggests.

Alice Shaw, from Massachusetts General Hospital in Boston, USA, and study co-authors explain that the primary cancer metastasises to the leptomeninges in approximately 4% of NSCLC patients with ALK translocations, but “the optimal management of this complication is poorly defined.”

In this case series, they describe four patients who were given alectinib at an initial dose of 600 mg twice daily as per a compassionate use protocol after developing symptomatic leptomeningeal disease during or following treatment with the ALK inhibitors crizotinib and ceritinib.

Leptomeningeal metastasis was defined as malignant cells in the patient’s cerebrospinal fluid or magnetic resonance imaging indicators of disease, such as leptomeningeal enhancement.

All patients responded to alectinib treatment, with improvements in symptoms such as headaches, diplopia, fatigue and right-sided weakness. Three patients also showed significant radiographical improvement of leptomeningeal disease, while the remaining patient had stable central nervous system (CNS) disease.

The treatment seemed to be generally well tolerated, say the researchers, with no significant toxicity in three participants. But one patient’s treatment was interrupted as a result of grade 2 hyperbilirubinaemia and the alectinib dose was reduced to 450 mg twice daily on resumption.

Two patients acquired resistance to alectinib during the course of their treatment, prompting the researchers to highlight the “the need for additional therapies or therapeutic combinations with activity in the CNS.”

The fact that alectinib has clinical activity in this patient population despite prior treatment with crizotinib and ceritinib indicates that alectinib may have “greater CNS activity”, Shaw et al write in the Journal of Thoracic Oncology.

They conclude: “Additional prospective studies of alectinib in ALK-positive patients with CNS metastases, including [leptomeningeal metastases], are therefore warranted.”

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