The Food and Drug Administration (FDA) has approved Alunbrig® (brigatinib; Takeda) as a first-line treatment of adults with anaplastic lymphoma kinase(ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
The approval was based on results from the phase 3 ALTA 1L trial that compared the efficacy and safety of brigatinib to crizotinib in 275 adult patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy. Patients were randomized to receive either brigatinib 90mg orally once daily for 7 days followed by 180mg once daily (n=137) or crizotinib 250mg orally twice daily (n=138) until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) for up to 36 months as assessed by a Blinded Independent Review Committee (BIRC). Key secondary end points included overall response rate (ORR) and intracranial ORR.
Results demonstrated that brigatinib met the primary end point achieving superiority over crizotinib with a median PFS of 24 months vs 11 months for crizotinib (hazard ratio [HR] 0.49; 95% CI, 0.35-0.68; P <.0001). In addition, confirmed ORR was 74% (95% CI, 66-81) with brigatinib vs 62% (95% CI, 53-70) with crizotinib (P =.0342). Moreover, brigatinib demonstrated a superior response in patients with measurable brain metastases with a confirmed intracranial ORR of 78% (95% CI, 52-94) vs 26% (95% CI, 53-70) with crizotinib.
The safety profile of brigatinib was consistent with that seen in previous studies. The most common adverse reactions (≥25%) included diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea.
“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for ALK+ lung cancer patients that have proven to be superior to crizotinib,” said Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research, University of Colorado Cancer Center. “Compared to crizotinib, brigatinib demonstrated superior efficacy, especially among those with brain metastases at baseline, and a low pill burden, at 1 pill a day, which is an important factor when we could be controlling disease for years.”
The FDA also approved a companion diagnostic for brigatinib, the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc).
For more information visit alunbrig.com.