Brigatinib Superior to Crizotinib for Frontline ALK+ NSCLC

by Cassie Homer
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First-line treatment with brigatinib appeared superior to crizotinib for the treatment of adults with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small cell lung cancer (NSCLC), according to result from the phase 3 ALA-1L trial presented at the European Society of Medical Oncology 2018 Congress.

“The ALK+ NSCLC treatment landscape has experienced tremendous change over the last decade, and the ALTA-1L trial demonstrates that brigatinib has the potential to be a key player in the first-line setting,” D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and the lead investigator of ALTA-1L, said in a press release.


​Lung Cancer. Source: iStock

The global, open-label ALTA-1L trial included 275 patients with ALK+ locally advanced or metastatic NSCLC who had not received prior treatment with an ALK inhibitor.

Researchers randomly assigned patients to 180 mg once daily brigatinib, with a seven-day lead in of 90 mg once daily (n = 137) or 250 mg twice daily crizotinib (n = 138).

“The ALTA-1L trial offers unique aspects, including the real-world applicability of the data,” Camidge said in the release. “The study’s design offered enrollment to a broader population by allowing patients to participate even if they had received prior chemotherapy and enrolled patients based on local standard of care ALK testing as opposed to mandating confirmation at a central lab.”

Results showed a 51% reduction in risk for death among patients treated with brigatinib compared with those treated with crizotinib (HR = 0.49; 95% CI, 0.33-0.74).

Brigatinib also had superior results among those with brain metastases at baseline (brigatinib, n = 43; crizotinib, n = 47).

Intracranial progression-free survival (PFS) was significantly improved among those treated with brigatinib (HR = 0.42; 95% CI, 0.24-0.7). Results also showed improved time to intracranial progression without prior systemic progression among those in the brigatinib group (HR = 0.3; 95% CI, 0.15-0.6) compared with the crizotinib group. The one-year cumulative incidence was 12% (95% CI, 6-20) among those treated with brigatinib compared with 23% (95% CI, 15-31) among those treated with crizotinib.

“We are thrilled to share these highly anticipated results with the lung cancer community,” David Kerstein, MD, global clinical lead for brigatinib and lung cancer clinical portfolio strategy lead at Takeda, said in the release. “The ALTA-1L data demonstrate that Alungbrig is superior to crizotinib in the first-line setting, reducing disease progression or death by more than half, with particularly pronounced activity in the brain.”