According to a new study published in the journal The Lancet Oncology, alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, may be effective treatment for patients with non-small cell lung cancer (NSCLC) refractory to crizotinib, another ALK inhibitor. In the phase 1 study, researchers tested alectinib in 47 patients with ALK-rearranged NSCLC. Patients received alectinib orally twice daily at dose between 300 and 900 mg. Patients initiated alectinib at a median of 18 days after the discontinuation of crizotinib.
After a median of 126 days, 55% of assessed patients had a response to alectinib. Of those, one patient achieved a complete response at a dose of 900 mg. Furthermore, 32% achieved a confirmed partial response, 20% had an unconfirmed partial response, and 36% had stable disease. About 9% experienced disease progression. Results also showed central nervous system metastasis activity with alectinib.
In regard to adverse effects, grade 3 headaches and grade 3 neutropenia led to dose reductions in patients taking the 900 mg dose. About 26% of patients required dose reductions or treatment interruption as a result of adverse events. The researchers suggest that the 600 mg twice daily dose of alectinib should be used for the phase 2 study.
“[A]lmost all patients with ALK-rearranged NSCLC invariably progress, with the CNS [central nervous system] being a common site of relapse”, note researcher Sai-Hong Ou (University of California Irvine School of Medicine, Orange, USA) and team. Progression in the CNS and resistance to crizotinib mean that “we urgently need novel ALK inhibitors that can overcome acquired ALK resistance, can cross the blood–brain barrier, and are well tolerated”, the researchers add.
In the current dose-finding part of the AF-002JG study, 47 patients with ALK-rearranged NSCLC began oral alectinib twice a day a median of 18 days after discontinuing crizotinib. The dose varied from 300 to 900 mg.