Brigatinib for the treatment of previously treated ALK-positive non-small-cell lung cancer

This trial examined a new therapy, brigatinib (Alunbrig), in treating patients with ALK-positive non-small-cell lung cancer (NSCLC) that has progressed passed initial treatments. The authors concluded that brigatinib was safe and effective at treating this type of cancer.

One type of NSCLC is caused by genetic changes in the ALK gene. There are specific treatments that target this type of cancer called ALK tyrosine kinase inhibitors (ALK inhibitors). Cancers caused by this genetic change usually develop further genetic changes which make them resistant to current ALK inhibitors. Cancer spreading to the brain is then common for this type of cancer. Therefore, new drugs that are active against a broader range of changes are needed. Brigatinib is a new ALK inhibitor which was designed to treat NSCLC with a broader range of genetic changes.

This study aims to determine the most effective and safest dose of brigatinib to use to treat NSCLC that has progressed passed initial treatments. These patients will therefore have a greater range of genetic changes.

222 patients were included in this study. 112 patients in group 1 were treated with 90 mg brigatinib daily. 110 patients in group 2 were treated with 90 mg brigatinib for the first 7 days, followed by 180 mg brigatinib. Patients were followed for an average of 8 months.

The objective response rate (ORR – patients with tumor size reduction) was 45% for group 1 patients and 54% for group 2 patients. Average time to disease progression was 9.2 months for patients in group 1 and 12.9 months for patients in group 2.

154 patients had cancer that had spread to the brain at the beginning of the trial. Of these patients, the ORR for group 1 patients was 42% and 67% for group 2 patients.

The most common side effects were nausea, diarrhea, headache and cough. These were mostly mild and similar between patient groups. More severe side effects included hypertension (high blood pressure) and pneumonia, which affected roughly 5% of patients. 3% of patients had moderate to severe side effects in the first week. There was no increase in side effects when patients were treated with 180 mg, however 20% of group 2 patients had dose changes.

The authors conclude that treating patients with 90 mg followed by an increase to 180 mg is safe and effective at treating this type of cancer.

This research was funded in part by ARIAD Pharmaceuticals, the manufacturers of brigatinib.