About 5% of cases of non-small-cell lung cancer are ALK-positive. Crizotinib has been the first medicine to target ALK specifically. It was approved by the FDA in 2011. Though the majority of patients benefit from crizotinib initially, the cancer typically progresses within a year. The newer anaplastic lymphoma kinase (ALK) inhibitor Alectinib has been shown to halt cancer growth for a median of 15 months longer with fewer severe side effects than Crizotinib, the standard of care, in ALK-positive non-small-cell lung cancer. Alectinib is a more potent, next-generation ALK inhibitor. It was approved initially in 2015 for advanced non-small-cell lung cancer that worsens despite crizotinib therapy.
In the first global study to compare Alectinib with Crizotinib in ALK-positive lung cancer Alectinib was established as the new standard of care for initial treatment in this setting. Alectinib was especially beneficial in controlling and preventing brain metastases, which can exert a major impact on quality of life.
Alectinib reduced the risk of cancer progression or death by 53% vs crizotinib. Based on independent review, alectinib extended the median time to progression by about 15 months (median progression-free survival 25.7 months with alectinib vs 10.4 months with crizotinib).
While both treatments cross the blood-brain barrier, alectinib was more effective in preventing brain metastases than crizotinib, because it penetrates the brain more effectively. After 12 months, the incidence of brain metastases was much lower with alectinib than with crizotinib (9% vs 41%).
Overall, severe side effects were less common with alectinib than with crizotinib, occurring in 41% vs 50% of patients. The most common side effects of alectinib were fatigue, constipation, muscle aches, and swelling; whereas crizotinib caused gastrointestinal problems and liver enzyme abnormalities.
The fact that this second-generation targeted treatment halts advanced lung cancer growth for more than 2 years while preventing brain metastases is a remarkable result in this difficult disease.
