Comparing the effectiveness and safety of first-line treatment options in patients with advanced ALK-rearranged NSCLC.

This study compared the effectiveness and safety of first-line treatment options in patients with advanced ALK-rearranged non-small-cell lung cancer (NSCLC). The data showed that alectinib (Alecensa) and lorlatinib (Lorbrena) were the most effective and safest first-line treatment options for these patients.

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 rearrangement in the ALK gene is responsible for about 2-7% of all NSCLCs. These cancers are referred to as ALK-rearranged NSCLC.

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, some patients experience resistance to treatment and disease progression. Ceritinib (Zykadia) and alectinib are newly developed ALK inhibitors that have been shown to be effective for NSCLC patients in terms of overall survival. However, there are very few studies comparing the effectiveness and safety of different first-line treatment options in patients with advanced ALK-rearranged NSCLC.

This study analyzed 9 studies that involved 2484 patients with advanced ALK-rearranged NSCLC. The 8 first-line treatment options analyzed were crizotinib, alectinib (300 mg), alectinib (600 mg), brigatinib (Alunbrig), lorlatinib, ensartinib (X-396), ceritinib, and chemotherapy.

Lorlatinib had the highest probability (63.7%) to be the best treatment regimen in terms of better survival without cancer progression followed by alectinib 300 mg (17.6%), and alectinib 600 mg (7.2%).

Alectinib 600 mg had the highest probability (35.9%) to be the best treatment regimen in terms of better overall survival followed by lorlatinib (30.6%) and ensartinib (11.8%).

Alectinib 300 mg had the highest probability (37%) to be the best treatment regimen in terms objective response rate (ORR; partial or complete disappearance of cancer) followed by lorlatinib (21%) and alectinib 600 mg (13%).

Ceritinib was associated with the highest rate of severe side effects (60%) followed by lorlatinib (18%). Alectinib 300 mg had the highest probability (59%) to be the safest treatment regimen followed by alectinib 600 mg (22%).

This study concluded that alectinib and lorlatinib were the most effective and safest first-line treatment options for patients with advanced ALK-rearranged NSCLC.

This study looked back in time at medical records. This study did not directly compare the different first-line treatment regimens and the average overall survival data was missing in some of the studies analyzed.