FDA approves Alunbrig for lung cancer subset
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The FDA approved brigatinib for first-line treatment of adults with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer.
Brigatinib (Alunbrig, Takeda) is a next-generation tyrosine kinase inhibitor designed to target anaplastic lymphoma kinase (ALK) molecular alterations. An estimated 3% to 5% of patients with metastatic NSCLC have ALK rearrangements.
“As with many forms of lung cancer, ALK-positive NSCLC is a complex and aggressive cancer that presents various treatment challenges for patients who are newly diagnosed, including those whose disease has spread to their brain,” Andrea Stern Ferris, president and CEO of LUNGevity Foundation, said in a Takeda-issued press release. “Having this option for newly diagnosed patients is exciting news for the ALK-positive NSCLC community and adds to the remarkable progress we have witnessed in lung cancer treatment over the past decade.”
The FDA previously approved brigatinib for treatment of patients with ALK-positive metastatic NSCLC who progressed on or could not tolerate crizotinib (Xalkori; Pfizer, EMD Serono).
The agency based the first-line indication on results of the randomized phase 3 ALTA 1L trial, which included 275 adults with ALK-positive locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor.
Researchers assigned 137 patients to brigatinib dosed at 180 mg once daily, with a 7-day lead-in at 90 mg once daily. The other 138 patients received crizotinib dosed at 250 mg orally once daily.
Treatment groups were comparable with regard to median age (58 years for brigatinib vs. 60 years for crizotinib), percentage of patients with brain metastases at baseline (29% vs. 30%) and percentage who had received prior chemotherapy for advanced or metastatic disease (26% vs. 27%).
PFS assessed by blinded independent review served as the major efficacy outcome. Additional efficacy outcomes included confirmed overall response rate and intracranial ORR.
After more than 2 years of follow-up, results showed improved PFS (median, 24 months vs. 11 months; HR = 0.49) and ORR (74% vs. 62%) among brigatinib-treated patients.
Among patients with measurable brain metastases at baseline, a higher percentage of those treated with brigatinib than crizotinib achieved confirmed intracranial response (78% vs. 26%).
The most common adverse reactions among brigatinib-treated patients included diarrhea (53%), rash (40%), cough (35%), hypertension (32%), fatigue (32%), nausea (30%), myalgia (28%), dyspnea (25%), abdominal pain (24%) and headache (22%).
One-third (33%) of patients assigned brigatinib experienced serious adverse events. The most common were pneumonia (4.4%), interstitial lung disease/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%) and asthenia (2.2%). Also, 2.9% of patients experienced fatal adverse reactions other than disease progression; these included pneumonia (1.5%), cerebrovascular accident (0.7%) and multiple organ dysfunction syndrome (0.7%).
“Results from the ALTA 1L trial add brigatinib to the very short list of first-line treatment options for [patients with ALK-positive lung cancer] that have proven to be superior to crizotinib,” D. Ross Camidge, MD, PhD, Joyce Zeff chair in lung cancer research at University of Colorado Cancer Center, said in the press release. “Compared to crizotinib, brigatinib demonstrated superior efficacy — especially among those with brain metastases at baseline — and a low pill burden, at one pill a day, which is an important factor when we could be controlling disease for years. These data have established brigatinib’s potential in the first-line setting, and I’m confident the FDA approval will open a new window of possibilities for physicians and their patients.”
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