Alectinib for advanced ALK-positive non-small-cell lung cancer.
PURPOSE
The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed.


SUMMARY
In patients with NSCLC driven by mutations of ALK, the gene coding for anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has been found to provide median progression-free survival (PFS) of 10.9 months; however, therapeutic failures and tumor progression to brain metastases are common with crizotinib use, prompting research to find more potent and tolerable ALK inhibitors that target major oncogenic drivers of NSCLC. Alectinib is a next-generation ALK inhibitor initially approved by the Food and Drug Administration for use in patients with metastatic ALK-positive NSCLC who are intolerant of or have disease progression during crizotinib therapy. In clinical trials, alectinib was found effective for delaying disease progression and, more importantly, reducing brain metastases in patients with NSCLC who developed resistance or intolerance to previous crizotinib therapy. Published data from clinical trials indicate that the most common grade 1 and 2 adverse effects associated with alectinib use are fatigue, constipation, peripheral edema, and myalgia; the most common grade 3 or 4 reactions include increases in creatine phosphokinase, alanine aminotransferase, and aspartate aminotransferase levels.


CONCLUSION
Alectinib appears to be effective and safe for use in patients with metastatic ALK-positive NSCLC, with demonstrated superiority over crizotinib in terms of PFS rates. Research to better define ALK inhibitor resistance mechanisms and alectinib's place in therapy is ongoing.
['Ly|Ashley C|AC|', 'Olin|Jacqueline L|JL|', 'Smith|Morgan B|MB|']
D000077548:Anaplastic Lymphoma Kinase D002227:Carbazoles D002289:Carcinoma, Non-Small-Cell Lung D018450:Disease Progression D018572:Disease-Free Survival D019008:Drug Resistance, Neoplasm D006801:Humans D008175:Lung Neoplasms D009154:Mutation D010880:Piperidines D047428:Protein Kinase Inhibitors
alectinib antineoplastic agents carcinoma, non-small-cell lung