- At the first planned interim analysis in the ALTA-1L phase 3 trial, the anaplastic lymphoma kinase (ALK) inhibitor brigatinib was superior to crizotinib in patients with ALK+ NSCLC.
Why this matters
- ALK+ NSCLC occurs most often in people
- ALK inhibitors can stop cancer cells from growing and spreading.
- The PROFILE 1014 phase 3 trial (NCT01154140) demonstrated efficacy of crizotinib vs chemotherapy in ALK+ NSCLC, but resistance has been reported.
- Brigatinib is a next-generation ALK/ROS1 inhibitor and endothelial growth factor inhibitor with promising PFS reported for ALK+ NSCLC in 2 small trials.
- Brigatinib may also delay brain metastasis.
- ALTA-1L (NCT02737501) phase 3, open-label randomized trial of 275 patients with ALK inhibitor-naive advanced ALK+ stage III/IV NSCLC.
- Patients received brigatinib 180 mg daily after a 7-day lead-in at 90 mg (n=137) or crizotinib (250 mg twice daily, n=138).
- Stratification included brain metastasis at baseline (yes or no) and prior chemotherapy for locally advanced or metastatic disease (yes or no).
- Primary endpoint: PFS.
- Key secondary endpoints: confirmed objective response rate, confirmed intracranial objective response rate, intracranial PFS, OS, safety, and tolerability.
- Disease assessment every 8 weeks, including brain MRI.
- Funding: Ariad Pharmaceuticals.
- Primary endpoint met: investigator-assessed median PFS was not yet reached in the brigatinib group vs 9.2 months (95% CI, 7.4-12.9 months) in the crizotinib group (HR, 0.45; 95% CI, 0.30-0.68; log-rank P=.0001).
- Superiority of brigatinib vs crizotinib evident in patients who had received prior chemotherapy (HR, 0.35; 95% CI, 0.14-0.85; log-rank P=.0207) and in those who had not received chemotherapy (HR, 0.55; 95% CI 0.34-0.88; log-rank P=.0095).
- Subgroup analysis indicated that the outcome might be better for patients with central nervous system (CNS) disease at baseline: prevalence of disease progression was 59% with crizotinib vs 20% with brigatinib (40% vs 29% in patients without baseline CNS disease).
- Brigatinib superior to crizotanib concerning intracranial PFS for patients with any brain metastasis at baseline (HR, 0.27; 95% CI, 0.13-0.54, P<.0001>
- Brigatinib well tolerated; dose reductions were mainly protocol-mandated for laboratory abnormalities
- "At the first planned interim analysis, brigatinib demonstrated superior PFS vs crizotinib. Brigatinib represents a promising new first-line treatment option for ALK-positive NSCLC," said presenter D. Ross Camidge, MD, PhD, University of Colorado Cancer Center, Aurora.