New targeted therapy for ALK-mutated lung cancer

This early phase trial investigated the safety and effect of ceritinib, a new ALK inhibitor, for the treatment of non-small cell lung cancer patients harboring mutations of the ALK gene.

Anaplastic lymphoma kinase (ALK) is an important protein involved in cell development. It is estimated that genetic changes that alter the function of ALK are responsible for about 5% of all non-small cell lung cancers. 

Crizotinib (Xalkori), the first developed ALK inhibitor, has been shown to successfully delay cancer progression and extend survival among patients. However, eventually patients experience resistance to treatment and disease progression.

Ceritinib (Zykadia) is a newly developed ALK inhibitor, and has been shown to be significantly more potent than crizotinib in pre-clinical trials. This study investigated the effects of ceritinib on ALK-mutated lung cancer patients, including those with progressed cancer despite previous crizotinib treatment.

The trial enrolled a total of 122 patients with advanced or metastatic non-small cell, ALK-mutated lung cancer, to be treated with various ceritinib dosages. Of these, 68% of patients had previously received crizotinib treatment but showed cancer progression.

The majority of patients (114) were able to tolerate an effective ceritinib dose of at least 400mg per day without significant side-effects. The most common side effects related to ceritinib treatment were nausea, diarrhea, vomiting, fatigue and liver function test anomalies. 

Among those patients who received at least 400 mg of ceritinib per day, 58% of patients showed response to treatment. Among the patients who had previously received crizotinib, 56% showed response to treatment. On average, progression-free survival (survival without evidence of further cancer progression) was 7 months, and was similar among patients who had or had not been previously treated with crizotinib.

Ceritinib was found to be safe and effective, even among patients previously treated with crizotinib. This research suggests that ceritinib may represent a new treatment option for patients who develop crizotinib resistance.

Larger clinical trials are required to confirm the long term efficacy and safety of ceritinib, specifically in the setting of crizotinib resistance. The trial was funded by Novartis Pharmaceuticals who developed ceritinib.

Ceritinib was recently approved by the FDA (United States Food and Drug Administration) for the treatment of crizotinib-resistant, ALK-mutated lung cancer patients. Consult with your physician regarding the risks and benefits of this new treatment option.