The US Food and Drug Administration (FDA) has approved brigatinib, a dual ALK and EGFR inhibitor, for the treatment of patients with ALK-positive non–small cell lung cancer (NSCLC) who progressed while receiving or are intolerant to crizotinib.1

Brigatinib was previously granted Breakthrough Therapy and Orphan Drug designation. This approval is contingent on verification of clinical benefit in a confirmatory trial.

The FDA approved brigatinib based on an open-label, noncomparative trail (ALTA; ClinicalTrials.gov Identifier: NCT02094573) of 222 patients with locally advanced or metastatic ALK-positive NSCLC. The trial demonstrated an overall response rate (ORR) of 48% (95% CI, 39-58) with 90 mg and 53% (95% CI, 43-62) with 180 mg of brigatinib by independent review.

The duration of response was 13.8 months during a median follow-up of 8 months.

Intracranial ORR was 42% (95% CI, 23-63) with 90 mg and 67% (95% CI, 41-87) with 180 mg of brigatinib among patients with brain metastases at baseline.

Adverse events (AEs) occurred in at least 25% of patients and were most commonly nausea, diarrhea, fatigue, cough, and headache. The most serious AEs were pneumonia and pneumonitis.

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AEs resulted in death in 3.7% of patients, caused by pneumonia, sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis.

Treatment discontinuation due to AEs occurred in 2.8% and 8.2% of patients in the 90 and 180 mg arms, respectively.

Reference

  1. Brigatinib [news release]. Silver Spring, MD: US Food and Drug Administration; April 28, 2017. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm555841.htm. Accessed April 28, 2017.