A recent study published in the Journal of Thoracic Oncology demonstrated that patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) responded positively to treatment with alectinib, an ALK inhibitor. The study is entitled “Alectinib Salvages CNS Relapses in ALK-Positive Lung Cancer Patients Previously Treated with Crizotinib and Ceritinib”.
ALK is an enzyme thought to help brain development by regulating the proliferation of nerve cells. Rearrangements in the ALK gene have been described in non-small cell lung cancer (NSCLC) and are seen as key therapeutic targets in NSCLC, as they confer sensitivity to ALK inhibitors.
Leptomeningeal metastases (LM) correspond to a cancer complication that has become more frequent and destructive in anaplastic lymphoma kinase (ALK)-rearranged NSCLC. LM is often a terminal condition in which cancer cells spread to the membranes (called meninges) surrounding the brain and spinal cord. LM in NSCLC is linked to a poor prognosis (median survival of 3 to 4.3 months) and its management in ALK-positive patients is still poorly defined.
The study focused on four ALK-positive NSCLC patients who developed LM during or after treatment with two ALK inhibitors: ceritinib and crizotinib. In the study, the four patients started therapy with a new, second-generation, highly potent ALK inhibitor, which has been shown to have antitumor activity in early phase clinical trials. This new drug is called alectinib and was given to patients twice a day at a 600 mg dose.
The researchers determined by clinical and radiographic assessments that three patients improved significantly after treatment with alectinib, while in the fourth patient the disease stabilized for 4 months before progressing. The inhibitor was well tolerated by the individuals without significant adverse events, although the dose had to be reduced for one of the patients as she developed grade 2 hyperbilirubinemia.
The study shows that alectinib has a significant antitumor activity and represents a successful therapy in ALK-positive NSCLC patients with LM, even if patients had undergone prior treatment with crizotinib and ceritinib. The research team suggests that the clinical success of alectinib may be related to its higher bioavailability and activity in the central nervous system when compared to other drugs.