The FDA has approved brigatinib (Alunbrig) for the treatment of metastatic ALK-positive non-small-cell lung cancer, specifically in patients who have progressed on or are intolerant to crizotinib.
The US Food and Drug Administration (FDA) announced approval of brigatinib (Alunbrig, Ariad Pharmaceuticals) for the treatment of metastatic anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC), specifically in patients who have progressed on or are intolerant to crizotinib.
The approval, which was granted under after an accelerated review, was announced yesterday. “In recent years, small molecule ALK inhibitors have revolutionized the treatment options for those with advanced ALK-positive NSCLC,” said D. Ross Camidge, MD, PhD, of the University of Colorado, in a press release from the drug’s developer. “Nevertheless, there is still a need for additional ALK inhibitors like brigatinib, which have a manageable safety profile and may address mechanisms of clinical resistance to crizotinib, including progression in the central nervous system.”
The approval was based on results of a two-arm, open-label trial known as the ALTA trial. Results were first presented in June 2016 at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
The trial included 222 patients with documented ALK rearrangement who had progressed on crizotinib; of those, 112 received a dose of 90 mg once daily, and 110 patients received a higher dose of 180 mg once daily following a 7-day lead-in at the lower dose. The study had a median follow-up of 8 months.
The overall response rate (ORR) according to independent review was 48% with the lower dose and 53% with the higher dose. The median duration of response was 13.8 months in both groups. Notably, in patients who had measurable brain metastases at baseline, the intracranial ORR was 42% with 90 mg brigatinib and 67% with 180 mg brigatinib. Among those with an intracranial response, 78% of those receiving the 90 mg dose and 68% of those receiving the 180 mg dose maintained that response for at least 4 months.
Safety of the agent was evaluable in 219 patients who received at least one dose. The most common adverse events included nausea, diarrhea, and fatigue, while the most common serious adverse events were pneumonia and interstitial lung disease/pneumonitis. Adverse events that led to permanent discontinuation of brigatinib occurred in 2.8% of lower-dose patients and 8.2% of higher-dose patients; fatal adverse events occurred in 3.7% of patients, and included pneumonia, sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis.
The FDA recommends a lead-in with the 90 mg dose, followed by an increase to 180 mg once daily if tolerated. “Today’s FDA approval of Alunbrig is an important milestone in the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib,” said Christophe Bianchi, MD, the president of Takeda Oncology; Takeda Pharmaceutical Company owns Ariad Pharmaceuticals.