Κυριακή, 30 Απριλίου 2017

BRIGATINIB APPROVED FOR ALK+ NSCLC

On April 28, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to brigatinib (Alunbrig) for the treatment of patients with metastatic anaplastic lymphoma kinase (ALK)-positive non­–small cell lung cancer (NSCLC) who have had disease progression on or are intolerant to crizotinib.
ALTA Trial
Approval was based on the noncomparative, two-arm, open-label, multicenter ALTA clinical trialdemonstrating a clinically meaningful and durable overall response rate in patients with locally advanced or metastatic ALK-positive NSCLC that had progressed during crizotinib therapy. All patients had tumors with a documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization Probe Kit test. A total of 222 patients were randomized to brigatinib orally at either 90 mg once daily (n = 112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (n = 110).
Overall response rate was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR was 48% (95% CI: 39%, 58%) in the 90-mg arm and 53% (95% confidence interval [CI] = 43%–62%) in the 180-mg arm. After a median follow-up of 8 months, median duration of response was 13.8 months in both arms. In patients with measurable brain metastases at baseline, the intracranial response rate was 42% (95% CI = 23%–63%) in the 90-mg arm (n = 26) and 67% (95% CI = 41%–87%) in the 180-mg arm (n = 18). Median intracranial duration of response was not estimable in the 90-mg arm and was 5.6 months in the 180-mg arm. Among patients who exhibited an intracranial response, 78% in the 90-mg arm and 68% in the 180-mg arm maintained an intracranial response for at least 4 months.
Adverse Reactions
Safety was evaluated in 219 patients who received at least one dose of brigatinib in the ALTA trial.
The most common adverse reactions, occurring in at least 25% of patients taking brigatinib, were nausea, diarrhea, fatigue, cough, and headache. Visual disturbances also occurred in patients receiving brigatinib. The most common serious adverse reactions were pneumonia and interstitial lung disease/pneumonitis.
Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia in 2 patients and sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis in 1 patient each. Adverse reactions leading to permanent discontinuation of brigatinib occurred in 2.8% and 8.2% of patients receiving 90 mg and 180 mg, respectively.
Patients receiving brigatinib should be monitored for new or worsening respiratory symptoms; hypertension; bradycardia; visual symptoms; and elevations in amylase, lipase, blood glucose, and creatine phosphokinase.
The recommended dosing regimen of brigatinib is 90 mg orally once daily for the first 7 days and then, if tolerated, an increase to 180 mg orally once daily.


Full prescribing information is available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208772lbl.pdf.

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