FDA grants priority review to brigatinib for first-line treatment of ALK-positive lung cancer
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The FDA granted priority review to brigatinib as first-line treatment for anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer, according to the agent’s manufacturer.
An estimated 3% to 5% of patients with metastatic NSCLC have a rearrangement in the anaplastic lymphoma kinase (ALK) gene.
Brigatinib (Alunbrig, Takeda) is a selective next-generation tyrosine kinase inhibitor that targets ALK genetic alterations.
The agent already is approved in the United States for treatment of patients with ALK-positive metastatic NSCLC who progressed on or are intolerant of crizotinib (Xalkori, Pfizer).
The FDA granted priority review for the first-line indication based on results of the randomized phase 3 ALTA-1L trial, which compared the efficacy and safety of brigatinib with crizotinib for patients with ALK-positive locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor.
The global, multicenter trial included 275 patients. Researchers assigned them to brigatinib dosed at 180 mg once daily with a 7-day lead-in at 90 mg once daily (n = 137) or crizotinib dosed at 250 mg twice daily (n = 138).
The brigatinib and crizotinib groups were balanced with regard to median age (58 years vs. 60 years), brain metastases at baseline (29% vs. 30%), and receipt of prior chemotherapy for advanced or metastatic disease (26% vs. 27%).
PFS assessed by blinded independent review served as the primary endpoint. Secondary endpoints included objective response rate, intracranial ORR, intracranial PFS, OS, safety and tolerability.
As Healio previously reported, results showed a significant median PFS benefit with brigatinib as assessed by blinded independent review (24 months vs. 11 months; HR = 0.49; 95% CI, 0.35-0.68) and investigator assessment (29.4 months vs. 9.2 months; HR = 0.43; 95% CI, 0.31-0.61).
Results also showed a significantly higher confirmed ORR (74% vs. 62%; P = .0342) and longer median duration of response (not estimable vs. 14 months) in the brigatinib group.
No new safety signals associated with brigatinib emerged during the ALTA-1L trial.
The most common grade 3 or higher treatment-emergent adverse events observed among brigatinib-treated patients included increased creatine phosphokinase (24.3%), increased lipase levels (14%) and hypertension (11.8%). The most common grade 3 or higher treatment-emergent adverse events in the crizotinib group included increased alanine aminotransferase (10.2%), increased aspartate aminotransferase (6.6%) and increased lipase levels (6.6%).
Patients assigned brigatinib appeared more than twice as likely to develop any-grade interstitial lung disease or pneumonitis (5.1% vs. 2.2%). They also were more likely to discontinue treatment due to adverse events (12.5% vs. 8.8%).
“ALK-positive NSCLC is a rare and serious form of lung cancer that is complex to treat. [Although] progress has been made, unmet needs still exist for the approximately 40,000 patients diagnosed with this disease worldwide each year,” Christopher Arendt, PhD, head of Takeda’s oncology therapeutic area unit, said in a company-issued press release. “[The priority review designation] is an important first step in expanding treatment options for people with ALK-positive metastatic NSCLC in the U.S., and we look forward to continuing to work with regulatory authorities around the world to bring Alunbrig to newly diagnosed patients.”
The FDA is expected to make a decision on brigatinib for the first-line indication by June 23.