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Posted by on May 30, 2021 in Lung cancer | 0 comments

In a nutshell

This study compared the effectiveness of ceritinib (Zykadia) and alectinib (Alecensa) in patients with ALK-positive non-small-cell lung cancer (NSCLC) who previously had a crizotinib (Xalkori) treatment failure. The data showed that both ceritinib and alectinib were effective in these patients.

Some background

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer. Some NSCLCs are associated with a rearrangement or switching (mutation), of the anaplastic lymphoma kinase (ALK) gene with another gene. ALK is an important protein involved in cell development. A mutation in the ALK gene is responsible for about 5% of all NSCLCs. These cancers are referred to as ALK-positive NSCLC.

ALK inhibitors block the activity of the ALK protein. Crizotinib, the first approved ALK inhibitor, successfully delays cancer progression and extends survival among patients. However, some patients experience resistance to treatment and disease progression.

Ceritinib and alectinib are newly developed ALK inhibitors that have been shown to be effective for patients with NSCLC in terms of overall survival. However, there are very few studies comparing the effectiveness of ceritinib with alectinib in ALK-positive NSCLC patients who previously had a crizotinib treatment failure.

Methods & findings

This study involved 65 patients with ALK-positive NSCLC who had crizotinib treatment failure. 43 patients received alectinib and 22 patients received ceritinib. The average follow-up period was 16.8 months for the alectinib group and 32 months for the ceritinib group.

The average 12-month survival rate without any progression of disease (PFS; progression-free survival) was 61% for the alectinib group and 54.5% for the ceritinib group. The average PFS time was 20.1 months in the alectinib group and 13.9 months in the ceritinib group. This difference was not considered significant. 

The overall response rate (ORR; partial or complete disappearance of the cancer) was slightly higher for patients in the alectinib group (73.2%) compared to those in the ceritinib group (50%).

Patients treated with alectinib were 90% less likely to experience cancer progression to the brain than those treated with ceritinib. Alectinib treatment was also 71% more effective compared to ceritinib in patients whose crizotinib treatment failure was due to intolerance than due to resistance.

The most common side effects in patients treated with alectinib were increased liver enzymes, muscle pain, and nausea. In patients treated with ceritinib, the most common side effects were diarrhea, vomiting, and nausea.

The bottom line

This study concluded that both alectinib and ceritinib were effective for the treatment of patients with ALK-positive NSCLC who previously had a crizotinib treatment failure. Alectinib treatment was more effective in patients in whom crizotinib treatment failed due to intolerance rather than resistance and in protecting against brain progression.

The fine print

The sample size was small and the study looked back in time at medical records. This might limit the conclusions.

Published By :

BMC cancer

Date :

Mar 24, 2021

Original Title :

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed.

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