FDA Approves Brigatinib for ALK+ Lung Cancer

Nick Mulcahy

April 28, 2017

The US Food and Drug Administration (FDA) granted accelerated approval today of the oral therapy brigatinib (Alunbrig, Takeda/Ariad) for the treatment of patients who have metastatic non–small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive and who have experienced disease progression on or are intolerant of crizotinib (Xalkori, Pfizer).

The new approval is based on clinically meaningful and durable overall response rates (ORRs) in patients with locally advanced or metastatic ALK-positive NSCLC whose disease progressed with crizotinib.

In the noncomparative, two-arm, open-label, multicenter ALTA clinical trial, 222 patients were randomly assigned to brigatinib orally at doses of 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).

Assessed by an independent review committee, the ORR was 48% (95% confidence interval [CI], 39% - 58%) in the 90-mg arm and 53% (95% 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.

Notably, all patients had tumors with a documented ALK rearrangement, determined on the basis of an FDA-approved test or another FISH test.

In patients with measurable brain metastases at baseline, intracranial ORR 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% of patients in the 90-mg arm and 68% of patients in the 180-mg arm maintained an intracranial response for at least 4 months.

Safety was evaluated in 219 patients who received at least one dose of brigatinib in the ALTA trial.

The most common adverse reactions (≥25% of patients) were nausea, diarrhea, fatigue, cough, and headache. 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 (two patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urosepsis (one patient each).

Visual disturbances also occurred in patients receiving the new drug. Adverse reactions leading to permanent discontinuance of brigatinib occurred in 2.8% and 8.2% of patients receiving 90-mg and 180-mg doses, respectively.

Clinicians should monitor patients for new or worsening respiratory symptoms, hypertension, bradycardia, visual symptoms, and elevations in amylase, lipase, blood glucose, and creatine phosphokinase levels.

The recommended dosing regimen is 90 mg once daily for 7 days; if tolerated, the regimen is then increased to 180 mg once daily.

Full prescribing information is available online.

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