Alectinib ( Alecensa ) is a second-generation, orally active, potent and highly selective inhibitor of anaplastic lymphoma kinase ( ALK ).
Alectinib is approved for the treatment of ALK fusion-gene positive, unresectable, advanced or recurrent non-small cell lung cancer ( NSCLC ) in Japan, where it has been given orphan drug designation.
Approval was based on a phase 1-2 study in ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC who received twice-daily Alectinib 300 mg.
In the phase 2 portion, 93.5 % of patients achieved an objective response. Treatment response was rapid, with a partial response achieved in two-thirds of patients within 3 weeks ( cycle 1 ).
Patient follow-up is ongoing, and after approximately 2 years, 19.6 % of patients had achieved a complete response, and the 2-year progression-free survival rate is 76 %.
During treatment with Alectinib ( median follow-up approximately 8 months ), there was no progression of CNS lesions among patients with known CNS metastases at baseline ( although prior radiation therapy may have confounded results ).
In preclinical models, Alectinib was active against most ALK fusion-gene mutations related to Crizotinib resistance, and preliminary results from clinical trials indicate efficacy in Crizotinib-refractory NSCLC.
Alectinib was generally well tolerated in clinical trials, and there were no treatment-related grade 4 adverse events or deaths.
The most common grade 3 treatment-related adverse events were decreased neutrophil counts and increased creatinine phosphokinase.
While more data are needed to confirm the efficacy of Alectinib and to evaluate its activity in Crizotinib-resistant disease, the drug provides a very promising option for the treatment of ALK-rearranged advanced non-small cell lung cancer. ( Xagena )
McKeage K, Drugs 2015;75:75-82