Comparing the effects of brigatinib versus crizotinib in patients with non-small cell lung carcinoma

The study evaluated outcomes of brigatinib (Alunbrig) versus crizotinib (Xalkori) in patients with non-small cell lung carcinoma (NSCLC) and anaplastic lymphoma kinase (ALK) mutations, who were previously not treated with ALK inhibitors (ALKI). The main finding was that brigatinib had better long-term outcomes compared to crizotinib in such patients.

Mutations or cancerous changes in the ALK gene can lead to NSCLC. Such patients are called ALK+. Patients with ALK+ NSCLC treated by crizotinib, a traditional ALKI, often experience relapse. Brigatinib is a newer ALKI. Progression-free survival (PFS) defines how long patients survive without cancer’s progress. Recently, brigatinib showed better PFS compared to crizotinib within 11 months in patients with ALK+ NSCLC. However, the long-term effects of brigatinib in these patients are unknown.

The study included 275 adult patients with ALK+ NSCLC. Patients had never received ALKI before. 137 of patients received 180mg of brigatinib once daily. 138 patients received 250mg of crizotinib twice daily. Patients were followed up for 24.9 months on average.

Brigatinib was associated with a 51% lower probability of no progression after 2 years compared to crizotinib. Patients in the brigatinib had a 48% probability of no progression after 2 years. This was compared with a 26% probability of no progression for crizotinib. 56% of patients in the brigatinib group were estimated to be alive without cancer progression after 2 years. This was compared to 24% of the crizotinib group.

74% of patients treated with brigatinib responded to treatment. This was compared to 62% of those treated with crizotinib. The response lasted for an average of 13.8 months for the crizotinib group. However, the brigatinib group kept responding when data were analyzed. Overall, 76% of patients on brigatinib and 74% on crizotinib were estimated to survive for 2 years.

The average time for reducing the quality-of-life (QoL) was 26.7 months for brigatinib and 8.3 months for crizotinib. The crizotinib group had 30% higher risks of poor QoL. The most common unwanted side effects were gastrointestinal, cough, and increased liver enzymes. 

The authors concluded that brigatinib had better long-term effectiveness, tolerability and QoL compared to crizotinib in patients with ALK+ NSCLC.

This study was a second round of analysis from a clinical trial. The trial is still active. This study received support from Takeda, the manufacturer of brigatinib.