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FDA grants accelerated approval to brigatinib for ALK–positive NSCLC
The FDA granted accelerated approval to brigatinib for the treatment of patients with metastatic anaplastic lymphoma kinase–positive non–small cell lung cancer who progressed on or are intolerant to crizotinib.
The FDA recommended a dose of 90 mg orally once daily for the first 7 days. After that, if tolerated, the dose can be increased to 180 mg orally once daily.
The agency based the approval on results of the noncomparative, two-arm, open-label, multicenter ALTA trial, which assessed the safety and efficacy of brigatinib (AP26113, Ariad) in 222 patients with locally advanced or metastatic ALK–positive NSCLC who progressed on crizotinib (Xalkori, Pfizer).
Researchers randomly assigned patients to 90 mg oral brigatinib once daily (n = 112) or 180 mg oral brigatinib once daily (n = 110) following a 7-day lead-in at 90 mg once daily.
Results showed overall response rates of 48% (95% CI, 39-58) in the 90-mg group and 53% (95% CI, 43-62) in the 180-mg group. After median follow-up of 8 months, median duration of response was 13.8 months in both arms.
An analysis of patients with measurable brain metastases at baseline revealed intracranial ORRs of 42% (95% CI, 23-63) in the 90-mg group and 67% (95% CI, 41-87) in the 180-mg group.
Median intracranial duration of response was not estimable in the 90-mg group and 5.6 months in the 180-mg group.
Among patients who exhibited an intracranial response, 78% of patients assigned 90-mg doses and 68% of patients assigned 180-mg doses maintained intracranial responses for at least 4 months.
The safety analysis included 219 patients. The most common adverse events included nausea, diarrhea, fatigue, cough and headache. The most common serious adverse reactions included pneumonia and ILD/pneumonitis.
Fatal adverse reactions occurred in 3.7% of patients. They included pneumonia, sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis.
Visual disturbances also occurred in brigatinib-treated patients.
Adverse reactions prompted treatment discontinuation for 2.8% of patients assigned the 90-mg dose and 8.2% of patients assigned the 180-mg dose.
Patients who receive brigatinib should be monitored for new or worsening respiratory symptoms, hypertension, bradycardia, visual symptoms, and elevations in amylase, lipase, blood glucose and creatine phosphokinase, according to the FDA.