Brigatinib Granted FDA Priority Review for ALK-Positive Metastatic NSCLC
Posted: Wednesday, March 4, 2020
The U.S. Food and Drug Administration (FDA) granted Priority Review designation for brigatinib as a first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC). Previously, brigatinib was given FDA accelerated approval status for patients with NSCLC who were resistant or intolerant to crizotinib. Brigatinib is a next-generation tyrosine kinase inhibitor that targets ALK genetic alterations.
Priority Review is based on the phase III ALTA-1L clinical trial results. This study compared brigatinib with crizotinib in 275 patients with ALK-positive locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Patients were randomly selected to receive an 180-mg daily dose of brigatinib with a 7-day lead in at 90 mg once daily (n = 137) or a 250-mg dose of crizotinib twice daily (n = 138).
The study met its primary endpoint, demonstrating that compared with crizotinib, brigatinib had a superior blinded independent review committee–assessed progression-free survival.
Secondary endpoints included objective response rate, intracranial objective response rate, intracranial progression-free survival, overall survival, safety, and tolerability. The safety profile of brigatinib in this trial was reported to be generally consistent with existing U.S. prescribing information.
The most common adverse drug reactions associated with brigatinib in the 90-mg group included nausea (33%), fatigue (29%), headache (28%), and dyspnea (27%). In those who received 90 to 180 mg, the most common adverse drug reactions included nausea (40%), diarrhea (38%), fatigue (36%), cough (34%), and headache (27%). Serious adverse reactions to brigatinib occurred in 38% of patients in the 90-mg group and 40% of patients in the 90-to-180-mg group. Serious adverse reactions included pneumonia (5.5% overall) and interstitial lung disease/pneumonitis (4.6% overall). Fatal adverse reactions affected 3.7% of patients and consisted of sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, pneumonia, and urosepsis.
