Ceritinib and crizotinib in ALK-mutated lung cancer patients. A perfect combination?

This study looked at whether crizotinib and then ceritinib helped improve survival rates in patients with lung cancer.

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 found in 3-5% of all non-small cell lung cancers. ALK inhibitors block the activity of the ALK protein.

Crizotinib (Xalkori), the first approved ALK inhibitor, successfully delays cancer progression and extends 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 (not tested on humans). 

This study investigated the effects of ceritinib and crizotinib on ALK-mutated lung cancer patients.

73 ALK-mutated patients with non-small cell lung cancer were included in this study. 95% of patients had a type of lung cancer called adenocarcinoma. All patients were treated with crizotinib followed by ceritinib. Patients were treated with crizotinib for an average of 25 days. The average time from the last crizotinib dose to the first ceritinib dose was also 25 days.

The average time following treatment before the disease progressed (known as the progression free survival time) was 8.2 months for patients on crizotinib and 7.8 months for ceritinib. This was the same for patients who used other treatments between crizotinib and ceritinib. When both drugs were used one after the other the average progression free survival time was 17.4 months.

Some patients had their cancer reassessed after treatment with crizotinib and ceritinib. The average progression free survival time was the same regardless of having an ALK mutation or not.

The overall survival time (time from treatment until death from any cause) of the ALK-mutated patients treated with crizotinib and then ceritinib was 49.4 months. In patients whose cancer had spread to their brains before their treatment with crizotinib the average survival rate was just over 42 months.

This study concluded that ceritinib is useful as an anti-tumor agent in ALK-mutated patients with non-small cell lung cancer who have resistance to crizotinib.

This study included a relatively small number of patients. A larger study of these drugs should take place in the future.

Also, several of the authors received sponsorship from the manufacturers of crizotinib and ceritinib.