A new drug for the treatment of metastatic ALK-positive NSCLC

The authors aimed to summarize the results of two clinical trials to determine the effectiveness of alectinib as treatment for ALK-mutation positive NSCLC that has progressed beyond crizotinib. They concluded that alectinib is a suitable drug to treat this patient population. This treatment was FDA approved in 2015.

Several non-small-cell lung cancers (NSCLC) are driven by the anaplastic lymphoma kinase (ALK) gene joining to another gene. Therefore, research has been invested into the creation of medications to inhibit (block) ALK. Crizotinib (Xalkori) is an example of an ALK inhibitor used in the treatment of NSCLC. However, resistance to this drug has emerged. In addition to resistance to treatments, ALK-mutation positive NSCLCs commonly spread to the brain. To combat this, an ALK ihibitor called alectinib (Alecensa) was created with the aim to treat ALK-mutation positive cancer that is local or that has spread to the brain. 

The authors aimed to summarize the evidence presented from two clinical trials examining alectinib effectiveness at treating ALK-mutation positive NSCLC that has spread to the central nervous system. The data from these two clinical trials led to the FDA granting accelerated approval of the drug. 

The clinical trials included a total of 225 patients with ALK-mutation positive NSCLC that was either at an advanced stage or had spread to other parts of the body. These patients had progressed beyond treatment with crizotinib. They assessed objective response rate (ORR; amount of patients with greater than 30% reduction in tumor size) and duration of response (DOR; time from beginning treatment until disease progression).

The ORRs were 38% and 44%. The DORs were 7.5 months and 11.2 months. 

51 patients had cancer that had spread to the CNS. In these patients, the CNS ORR was 61% and DOR was 9.1 months.

The most common side effects were fatigue (41%), constipation (34%), swelling (30%) and muscle pain (29%). 12% of patients had the dose of the drug reduced. 6% of patients had treatment stopped due to treatment related side effects. 

The authors concluded that alectinib was effective in treating patients with ALK-positive mutation NSCLC that had progressed beyond crizotinib. The CNS ORR and DOR indicated that alectinib was effective at treating cancer that had spread to the CNS. 

One limitation of these trials is that they do not compare alectinib to another currently used drug. However, an ongoing trial is examining the effectiveness of alectinib versus crizotinib in patients who have not been previously treated with ALK inhibitor drugs.